Advertisement

Hematolymphoid System

  • John Choi
  • Jeffery M. Klco
  • Kamran Mirza
Chapter
Part of the Molecular Pathology Library book series (MPLB)

Abstract

Hematolymphoid neoplasm is the most common type of pediatric cancer and is classified by morphologic and immunophenotypic similarities to their normal counterparts, by their clinical presentation, and by their genetic mutations. Our understanding of the last is increasing dramatically and forms the basis for the latest subclassification of hematolymphoid neoplasms that provides better prediction of outcome and rationale for altered therapy. This chapter reviews our current classification scheme for pediatric hematolymphoid neoplasm.

Keywords

Childhood leukemia AML ALL Ph-like ALL CML BCR-ABL1 Leukemia associated with Down syndrome GATA1 Juvenile myelomonocytic leukemia Childhood myelodysplastic syndrome Therapy-related myeloid neoplasms Minimal residual disease Childhood lymphoma Next-generation sequencing NGS 

References

  1. 1.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman J, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008.Google Scholar
  2. 2.
    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.  https://doi.org/10.1182/blood-2016-03-643544.CrossRefPubMedGoogle Scholar
  3. 3.
    Guy J, Antony-Debre I, Benayoun E, Arnoux I, Fossat C, Le Garff-Tavernier M, Raimbault A, Imbert M, Maynadie M, Lacombe F, Bene MC, Wagner-Ballon O, GEIL. Flow cytometry thresholds of myeloperoxidase detection to discriminate between acute lymphoblastic or myeloblastic leukaemia. Br J Haematol. 2013;161(4):551–5.  https://doi.org/10.1111/bjh.12277.CrossRefPubMedGoogle Scholar
  4. 4.
    Matutes E, Morilla R, Farahat N, Carbonell F, Swansbury J, Dyer M, Catovsky D. Definition of acute biphenotypic leukemia. Haematologica. 1997;82(1):64–6.PubMedGoogle Scholar
  5. 5.
    Thalhammer-Scherrer R, Mitterbauer G, Simonitsch I, Jaeger U, Lechner K, Schneider B, Fonatsch C, Schwarzinger I. The immunophenotype of 325 adult acute leukemias: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination. Am J Clin Pathol. 2002;117(3):380–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Dong HY, Kung JX, Bhardwaj V, McGill J. Flow cytometry rapidly identifies all acute promyelocytic leukemias with high specificity independent of underlying cytogenetic abnormalities. Am J Clin Pathol. 2011;135(1):76–84.  https://doi.org/10.1309/AJCPW9TSLQNCZAVT.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhou Y, You MJ, Young KH, Lin P, Lu G, Medeiros LJ, Bueso-Ramos CE. Advances in the molecular pathobiology of B-lymphoblastic leukemia. Hum Pathol. 2012;43(9):1347–62.  https://doi.org/10.1016/j.humpath.2012.02.004.CrossRefPubMedGoogle Scholar
  8. 8.
    Sawinska M, Ladon D. Mechanism, detection and clinical significance of the reciprocal translocation t(12;21)(p12;q22) in the children suffering from acute lymphoblastic leukaemia. Leuk Res. 2004;28(1):35–42.CrossRefPubMedGoogle Scholar
  9. 9.
    Aspland SE, Bendall HH, Murre C. The role of E2A-PBX1 in leukemogenesis. Oncogene. 2001;20(40):5708–17.  https://doi.org/10.1038/sj.onc.1204592.CrossRefPubMedGoogle Scholar
  10. 10.
    Bernt KM, Hunger SP. Current concepts in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. Front Oncol. 2014;4:54.  https://doi.org/10.3389/fonc.2014.00054.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Meeker TC, Hardy D, Willman C, Hogan T, Abrams J. Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia. Blood. 1990;76(2):285–9.PubMedGoogle Scholar
  12. 12.
    Marschalek R. Mechanisms of leukemogenesis by MLL fusion proteins. Br J Haematol. 2011;152(2):141–54.  https://doi.org/10.1111/j.1365-2141.2010.08459.x.CrossRefPubMedGoogle Scholar
  13. 13.
    Hess JL. MLL: a histone methyltransferase disrupted in leukemia. Trends Mol Med. 2004;10(10):500–7.  https://doi.org/10.1016/j.molmed.2004.08.005.CrossRefPubMedGoogle Scholar
  14. 14.
    Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, Chen SC, Payne-Turner D, Churchman ML, Harvey RC, Chen X, Kasap C, Yan C, Becksfort J, Finney RP, Teachey DT, Maude SL, Tse K, Moore R, Jones S, Mungall K, Birol I, Edmonson MN, Hu Y, Buetow KE, Chen IM, Carroll WL, Wei L, Ma J, Kleppe M, Levine RL, Garcia-Manero G, Larsen E, Shah NP, Devidas M, Reaman G, Smith M, Paugh SW, Evans WE, Grupp SA, Jeha S, Pui CH, Gerhard DS, Downing JR, Willman CL, Loh M, Hunger SP, Marra MA, Mullighan CG. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell. 2012;22(2):153–66.  https://doi.org/10.1016/j.ccr.2012.06.005.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Harrison CJ, Moorman AV, Schwab C, Carroll AJ, Raetz EA, Devidas M, Strehl S, Nebral K, Harbott J, Teigler-Schlegel A, Zimmerman M, Dastuge N, Baruchel A, Soulier J, Auclerc MF, Attarbaschi A, Mann G, Stark B, Cazzaniga G, Chilton L, Vandenberghe P, Forestier E, Haltrich I, Raimondi SC, Parihar M, Bourquin JP, Tchinda J, Haferlach C, Vora A, Hunger SP, Heerema NA, Haas OA, Ponte di Legno International Workshop in Childhood Acute Lymphoblastic Leukemia. An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome. Leukemia. 2014;28(5):1015–21.  https://doi.org/10.1038/leu.2013.317.CrossRefPubMedGoogle Scholar
  16. 16.
    Schultz KR, Pullen DJ, Sather HN, Shuster JJ, Devidas M, Borowitz MJ, Carroll AJ, Heerema NA, Rubnitz JE, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Gaynon PS, Camitta BM. Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children’s Cancer Group (CCG). Blood. 2007;109(3):926–35.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Paulsson K, Lilljebjorn H, Biloglav A, Olsson L, Rissler M, Castor A, Barbany G, Fogelstrand L, Nordgren A, Sjogren H, Fioretos T, Johansson B. The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Nat Genet. 2015;47(6):672–6.  https://doi.org/10.1038/ng.3301.CrossRefPubMedGoogle Scholar
  18. 18.
    Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Vadodaria B, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Huether R, Lu C, Fulton RS, Fulton LL, Tabib Y, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Roberts AW, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Ellison DW, Shurtleff SA, Pui CH, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet. 2013;45(3):242–52.  https://doi.org/10.1038/ng.2532.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Tijchon E, Havinga J, van Leeuwen FN, Scheijen B. B-lineage transcription factors and cooperating gene lesions required for leukemia development. Leukemia. 2013;27(3):541–52.  https://doi.org/10.1038/leu.2012.293.CrossRefPubMedGoogle Scholar
  20. 20.
    Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, Lander ES, Golub TR, Look AT. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 2002;1(1):75–87.CrossRefGoogle Scholar
  21. 21.
    Van Vlierberghe P, Ferrando A. The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest. 2012;122(10):3398–406.  https://doi.org/10.1172/JCI61269.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Karrman K, Johansson B. Pediatric T-cell acute lymphoblastic leukemia. Genes Chromosom Cancer. 2016.  https://doi.org/10.1002/gcc.22416.
  23. 23.
    Paganin M, Ferrando A. Molecular pathogenesis and targeted therapies for NOTCH1-induced T-cell acute lymphoblastic leukemia. Blood Rev. 2011;25(2):83–90.  https://doi.org/10.1016/j.blre.2010.09.004.CrossRefPubMedGoogle Scholar
  24. 24.
    Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, Cheng C, Su X, Rubnitz JE, Basso G, Biondi A, Pui CH, Downing JR, Campana D. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147–56.  https://doi.org/10.1016/S1470-2045(08)70314-0.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481(7380):157–63.  https://doi.org/10.1038/nature10725.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Wood BL, Winter SS, Dunsmore KP, Devidas M, Chen S, Asselin B, Esiashvili N, Loh ML, Winick NJ, Carroll WL, Raetz EA, Hunger SP. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early thymic precursor (ETP) immunophenotype, and validation of the prognostic value of end-induction minimal residual disease (MRD) in Children’s Oncology Group (COG) Study AALL0434. Blood. 2014;124(21):1.Google Scholar
  27. 27.
    Jain N, Lamb AV, O'Brien S, Ravandi F, Konopleva M, Jabbour E, Zuo Z, Jorgensen J, Lin P, Pierce S, Thomas D, Rytting M, Borthakur G, Kadia T, Cortes J, Kantarjian HM, Khoury JD. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood. 2016;127(15):1863–9.  https://doi.org/10.1182/blood-2015-08-661702.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK, Cancer Research Institute Adult Leukaemia Working Group. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354–65.  https://doi.org/10.1182/blood-2009-11-254441.CrossRefPubMedGoogle Scholar
  29. 29.
    Manola KN. Cytogenetics of pediatric acute myeloid leukemia. Eur J Haematol. 2009;83(5):391–405.  https://doi.org/10.1111/j.1600-0609.2009.01308.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Radhi M, Meshinchi S, Gamis A. Prognostic factors in pediatric acute myeloid leukemia. Curr Hematol Malig Rep. 2010;5(4):200–6.  https://doi.org/10.1007/s11899-010-0060-z.CrossRefPubMedGoogle Scholar
  31. 31.
    Radtke I, Mullighan CG, Ishii M, Su X, Cheng J, Ma J, Ganti R, Cai Z, Goorha S, Pounds SB, Cao X, Obert C, Armstrong J, Zhang J, Song G, Ribeiro RC, Rubnitz JE, Raimondi SC, Shurtleff SA, Downing JR. Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia. Proc Natl Acad Sci U S A. 2009;106(31):12944–9.  https://doi.org/10.1073/pnas.0903142106.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Licht JD. AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML. Oncogene. 2001;20(40):5660–79.  https://doi.org/10.1038/sj.onc.1204593.CrossRefPubMedGoogle Scholar
  33. 33.
    Sanden C, Gullberg U. The DEK oncoprotein and its emerging roles in gene regulation. Leukemia. 2015;29(8):1632–6.  https://doi.org/10.1038/leu.2015.72.CrossRefPubMedGoogle Scholar
  34. 34.
    Braoudaki M, Papathanassiou C, Katsibardi K, Tourkadoni N, Karamolegou K, Tzortzatou-Stathopoulou F. The frequency of NPM1 mutations in childhood acute myeloid leukemia. J Hematol Oncol. 2010;3:41.  https://doi.org/10.1186/1756-8722-3-41.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Brown P, McIntyre E, Rau R, Meshinchi S, Lacayo N, Dahl G, Alonzo TA, Chang M, Arceci RJ, Small D. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood. 2007;110(3):979–85.  https://doi.org/10.1182/blood-2007-02-076604.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, Heerema NA, Hirsch B, Raimondi SC, Lange B, Franklin JL, Radich JP, Meshinchi S. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group. Blood. 2009;113(26):6558–66.  https://doi.org/10.1182/blood-2008-10-184747.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, Linda S, Martin PL, Pullen DJ, Viswanatha D, Willman CL, Winick N, Camitta BM. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood\. 2008;111(12):5477–85.  https://doi.org/10.1182/blood-2008-01-132837.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Coustan-Smith E, Sancho J, Hancock ML, Boyett JM, Behm FG, Raimondi SC, Sandlund JT, Rivera GK, Rubnitz JE, Ribeiro RC, Pui CH, Campana D. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood. 2000;96(8):2691–6.PubMedGoogle Scholar
  39. 39.
    Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, Pounds S, Razzouk BI, Lacayo NJ, Cao X, Meshinchi S, Degar B, Airewele G, Raimondi SC, Onciu M, Coustan-Smith E, Downing JR, Leung W, Pui CH, Campana D. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010;11(6):543–52.  https://doi.org/10.1016/S1470-2045(10)70090-5.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Loken MR, Alonzo TA, Pardo L, Gerbing RB, Raimondi SC, Hirsch BA, Ho PA, Franklin J, Cooper TM, Gamis AS, Meshinchi S, et al. Blood. 2012;120(8):1581–8.  https://doi.org/10.1182/blood-2012-02-408336.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Malec M, van der Velden VH, Bjorklund E, Wijkhuijs JM, Soderhall S, Mazur J, Bjorkholm M, Porwit-MacDonald A. Analysis of minimal residual disease in childhood acute lymphoblastic leukemia: comparison between RQ-PCR analysis of Ig/TcR gene rearrangements and multicolor flow cytometric immunophenotyping. Leukemia. 2004;18(10):1630–6.  https://doi.org/10.1038/sj.leu.2403444.CrossRefPubMedGoogle Scholar
  42. 42.
    Inaba H, Coustan-Smith E, Cao X, Pounds SB, Shurtleff SA, Wang KY, Raimondi SC, Onciu M, Jacobsen J, Ribeiro RC, Dahl GV, Bowman WP, Taub JW, Degar B, Leung W, Downing JR, Pui CH, Rubnitz JE, Campana D. Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia. J Clin Oncol. 2012;30(29):3625–32.  https://doi.org/10.1200/JCO.2011.41.5323.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Wu D, Sherwood A, Fromm JR, Winter SS, Dunsmore KP, Loh ML, Greisman HA, Sabath DE, Wood BL, Robins H. High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia. Sci Transl Med. 2012;4(134):134ra63.  https://doi.org/10.1126/scitranslmed.3003656.CrossRefPubMedGoogle Scholar
  44. 44.
    Faham M, Zheng J, Moorhead M, Carlton VE, Stow P, Coustan-Smith E, Pui CH, Campana D. Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2012;120(26):5173–80.  https://doi.org/10.1182/blood-2012-07-444042.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, Patel Y, Bhudia N, Farah H, Mason J, Wall K, Akiki S, Griffiths M, Solomon E, McCaughan F, Linch DC, Gale RE, Vyas P, Freeman SD, Russell N, Burnett AK, Grimwade D. Assessment of minimal residual disease in standard-risk AML. N Engl J Med. 2016;374(5):422–33.  https://doi.org/10.1056/NEJMoa1507471.CrossRefPubMedGoogle Scholar
  46. 46.
    Klco JM, Miller CA, Griffith M, Petti A, Spencer DH, Ketkar-Kulkarni S, Wartman LD, Christopher M, Lamprecht TL, Helton NM, Duncavage EJ, Payton JE, Baty J, Heath SE, Griffith OL, Shen D, Hundal J, Chang GS, Fulton R, O’Laughlin M, Fronick C, Magrini V, Demeter RT, Larson DE, Kulkarni S, Ozenberger BA, Welch JS, Walter MJ, Graubert TA, Westervelt P, Radich JP, Link DC, Mardis ER, DiPersio JF, Wilson RK, Ley TJ. Association between mutation clearance after induction therapy and outcomes in acute myeloid leukemia. JAMA. 2015;314(8):811–22.  https://doi.org/10.1001/jama.2015.9643.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Gruber TA, Downing JR. The biology of pediatric acute megakaryoblastic leukemia. Blood. 2015;126(8):943–9.  https://doi.org/10.1182/blood-2015-05-567859.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, Sanada M, Park MJ, Terui K, Suzuki H, Kon A, Nagata Y, Sato Y, Wang R, Shiba N, Chiba K, Tanaka H, Hama A, Muramatsu H, Hasegawa D, Nakamura K, Kanegane H, Tsukamoto K, Adachi S, Kawakami K, Kato K, Nishimura R, Izraeli S, Hayashi Y, Miyano S, Kojima S, Ito E, Ogawa S. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45(11):1293–9.  https://doi.org/10.1038/ng.2759.CrossRefPubMedGoogle Scholar
  49. 49.
    Andolina JR, Neudorf SM, Corey SJ. How I treat childhood CML. Blood. 2012;119(8):1821–30.  https://doi.org/10.1182/blood-2011-10-380774.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Karalexi MA, Baka M, Ryzhov A, Zborovskaya A, Dimitrova N, Zivkovic S, Eser S, Antunes L, Sekerija M, Zagar T, Bastos J, Demetriou A, Agius D, Florea M, Coza D, Polychronopoulou S, Stiakaki E, Moschovi M, Hatzipantelis E, Kourti M, Graphakos S, Pombo-de-Oliveira MS, Adami HO, Petridou ET. Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America. Eur J Cancer. 2016;67:183–90.  https://doi.org/10.1016/j.ejca.2016.08.011.CrossRefPubMedGoogle Scholar
  51. 51.
    Wang Y, Huang J, Rong L, Wu P, Kang M, Zhang X, Lu Q, Fang Y. Impact of age on the survival of pediatric leukemia: an analysis of 15083 children in the SEER database. Oncotarget. 2016.  https://doi.org/10.18632/oncotarget.11765.
  52. 52.
    Chang TY, Dvorak CC, Loh ML. Bedside to bench in juvenile myelomonocytic leukemia: insights into leukemogenesis from a rare pediatric leukemia. Blood. 2014;124(16):2487–97.  https://doi.org/10.1182/blood-2014-03-300319.CrossRefPubMedGoogle Scholar
  53. 53.
    Arico M, Biondi A, Pui CH. Juvenile myelomonocytic leukemia. Blood. 1997;90(2):479–88.PubMedGoogle Scholar
  54. 54.
    Niemeyer CM, Arico M, Basso G, Biondi A, Rajnoldi AC, Creutzig U, Haas O, Harbott J, Hasle H, Kerndrup G, Locatelli F, Mann G, StollmannGibbels B, van’t Veer-Korthof ET, van Wering E, Zimmermann M. Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. Blood. 1997;89(10):3534–43.PubMedGoogle Scholar
  55. 55.
    Locatelli F, Niemeyer CM. How I treat juvenile myelomonocytic leukemia. Blood. 2015;125(7):1083–90.  https://doi.org/10.1182/blood-2014-08-550483.CrossRefPubMedGoogle Scholar
  56. 56.
    Loh ML. Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia. Br J Haematol. 2011;152(6):677–87.  https://doi.org/10.1111/j.1365-2141.2010.08525.x.CrossRefPubMedGoogle Scholar
  57. 57.
    Sakaguchi H, Okuno Y, Muramatsu H, Yoshida K, Shiraishi Y, Takahashi M, Kon A, Sanada M, Chiba K, Tanaka H, Makishima H, Wang XA, Xu YY, Doisaki S, Hama A, Nakanishi K, Takahashi Y, Yoshida N, Maciejewski JP, Miyano S, Ogawa S, Kojima S. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia. Nat Genet. 2013;45(8):937–U140.  https://doi.org/10.1038/ng.2698.CrossRefPubMedGoogle Scholar
  58. 58.
    Caye A, Strullu M, Guidez F, Cassinat B, Gazal S, Fenneteau O, Lainey E, Nouri K, Nakhaei-Rad S, Dvorsky R, Lachenaud J, Pereira S, Vivent J, Verger E, Vidaud D, Galambrun C, Picard C, Petit A, Contet A, Poiree M, Sirvent N, Mechinaud F, Adjaoud D, Paillard C, Nelken B, Reguerre Y, Bertrand Y, Haussinger D, Dalle JH, Ahmadian MR, Baruchel A, Chomienne C, Cave H. Juvenile myelomonocytic leukemia displays mutations in components of the RAS pathway and the PRC2 network. Nat Genet. 2015;47(11):1334–40.  https://doi.org/10.1038/ng.3420.CrossRefPubMedGoogle Scholar
  59. 59.
    Stieglitz E, Taylor-Weiner AN, Chang TY, Gelston LC, Wang YD, Mazor T, Esquivel E, Yu A, Seepo S, Olsen SR, Rosenberg M, Archambeault SL, Abusin G, Beckman K, Brown PA, Briones M, Carcamo B, Cooper T, Dahl GV, Emanuel PD, Fluchel MN, Goyal RK, Hayashi RJ, Hitzler J, Hugge C, Liu YL, Messinger YH, Mahoney DH, Monteleone P, Nemecek ER, Roehrs PA, Schore RJ, Stine KC, Takemoto CM, Toretsky JA, Costello JF, Olshen AB, Stewart C, Li YJ, Ma J, Gerbing RB, Alonzo TA, Getz G, Gruber TA, Golub TR, Stegmaier K, Loh ML. The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet. 2015;47(11):1326–33.  https://doi.org/10.1038/ng.3400.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Stieglitz E, Troup CB, Gelston LC, Haliburton J, Chow ED, Yu KB, Akutagawa J, Taylor-Weiner AN, Liu YL, Wang YD, Beckman K, Emanuel PD, Braun BS, Abate A, Gerbing RB, Alonzo TA, Loh ML. Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia. Blood. 2015;125(3):516–24.  https://doi.org/10.1182/blood2014-09-601690.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Olk-Batz C, Poetsch AR, Nollke P, Claus R, Zucknick M, Sandrock I, Witte T, Strahm B, Hasle H, Zecca M, Stary J, Bergstraesser E, De Moerloose B, Trebo M, van den Heuvel-Eibrink MM, Wojcik D, Locatelli F, Plass C, Niemeyer CM, Flotho C, European Working Group of Myelodysplastic Syndromes in Childhood (EWOG-MDS). Aberrant DNA methylation characterizes juvenile myelomonocytic leukemia with poor outcome. Blood. 2011;117(18):4871–80.  https://doi.org/10.1182/blood-2010-8-298968.CrossRefPubMedGoogle Scholar
  62. 62.
    Furlan I, Batz C, Flotho C, Mohr B, Luebbert M, Suttorp M, Niemeyer CM. Intriguing response to azacitidine in a patient with juvenile myelomonocytic leukemia and monosomy 7. Blood. 2009;113(12):2867–8.CrossRefPubMedGoogle Scholar
  63. 63.
    Matsuda K, Shimada A, Yoshida N, Ogawa A, Watanabe A, Yajima S, Iizuka S, Koike K, Yanai F, Kawasaki K, Yanagimachi M, Kikuchi A, Ohtsuka Y, Hidaka E, Yamauchi K, Tanaka M, Yanagisawa R, Nakazawa Y, Shiohara M, Manabe A, Kojima S, Koike K. Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. Blood. 2007;109(12):5477–80.  https://doi.org/10.1182/blood-2006-09-046649.CrossRefPubMedGoogle Scholar
  64. 64.
    Niemeyer CM, Kang MW, Shin DH, Furlan I, Erlacher M, Bunin NJ, Bunda S, Finklestein JZ, Sakamoto KM, Gorr TA, Mehta P, Schmid I, Kropshofer G, Corbacioglu S, Lang PJ, Klein C, Schlegel PG, Heinzmann A, Schneider M, Stary J, van den Heuvel-Eibrink MM, Hasle H, Locatelli F, Sakai D, Archambeault S, Chen L, Russell RC, Sybingco SS, Ohh M, Braun BS, Flotho C, Loh ML. Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet. 2010;42(9):794–U93.  https://doi.org/10.1038/ng.641.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001;29(4):465–8.  https://doi.org/10.1038/ng772.CrossRefPubMedGoogle Scholar
  66. 66.
    Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A, Bos JM, Ommen SR, Esposito G, Lepri F, Faul C, Mundel P, Siguero JPL, Tenconi R, Selicorni A, Rossi C, Mazzanti L, Torrente I, Marino B, Digilio MC, Zampino G, Ackerman MJ, Dallapiccola B, Tartaglia M, Gelb BD. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007;39(8):1007–12.  https://doi.org/10.1038/ng2073.CrossRefPubMedGoogle Scholar
  67. 67.
    Tartaglia M, Pennacchio LA, Zhao C, Yadav KK, Fodale V, Sarkozy A, Pandit B, Oishi K, Martinelli S, Schackwitz W, Ustaszewska A, Martin J, Bristow J, Carta C, Lepri F, Neri C, Vasta I, Gibson K, Curry CJ, Siguero JPL, Digilio MC, Zampino G, Dallapiccola B, Bar-Sagi D, Gelb BD. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet. 2007;39(1):75–9.  https://doi.org/10.1038/ng1939.CrossRefPubMedGoogle Scholar
  68. 68.
    Chen PC, Yin JI, Yu HW, Yuan T, Fernandez M, Yung CK, Trinh QM, Peltekova VD, Reid JG, Tworog-Dube E, Morgan MB, Muzny DM, Stein L, McPherson JD, Roberts AE, Gibbs RA, Neel BG, Kucherlapati R. Next-generation sequencing identifies rare variants associated with Noonan syndrome. Proc Natl Acad Sci U S A. 2014;111(31):11473–8.  https://doi.org/10.1073/pnas.1324128111.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Bain BJ. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Haematologica. 2010;95(5):696–8.  https://doi.org/10.3324/haematol.2009.021675.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Hasle H, Kerndrup G, Jacobsen BB. Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia. 1995;9(9):1569–72.PubMedGoogle Scholar
  71. 71.
    Hasle H, Wadsworth LD, Massing BG, McBride M, Schultz KR. A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada. Br J Haematol. 1999;106(4):1027–32.CrossRefPubMedGoogle Scholar
  72. 72.
    Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR, Stary J, Schmitt-Graeff A, Fischer A, Harbott J, Chessells JM, Hann I, Fenu S, Rajnoldi AC, Kerndrup G, Van Wering E, Rogge T, Nollke P, Niemeyer CM. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood. 2003;102(6):1997–2003.  https://doi.org/10.1182/blood-2002-11-3444.CrossRefPubMedGoogle Scholar
  73. 73.
    Bader-Meunier B, Mielot F, Tchernia G, Buisine J, Delsol G, Duchayne E, Lemerle S, Leverger G, de Lumley L, Manel AM. Myelodysplastic syndromes in childhood: report of 49 patients from a French multicentre study. French Society of Paediatric Haematology and Immunology. Br J Haematol. 1996;92(2):344–50.CrossRefPubMedGoogle Scholar
  74. 74.
    Luna-Fineman S, Shannon KM, Atwater SK, Davis J, Masterson M, Ortega J, Sanders J, Steinherz P, Weinberg V, Lange BJ. Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients. Blood. 1999;93(2):459–66.PubMedGoogle Scholar
  75. 75.
    Antillon F, Raimondi SC, Fairman J, Liang H, Nagarajan L, Head D, Ribeiro RC. 5q- in a child with refractory anemia with excess blasts: similarities to 5q- syndrome in adults. Cancer Genet Cytogenet. 1998;105(2):119–22.CrossRefPubMedGoogle Scholar
  76. 76.
    Gohring G, Michalova K, Beverloo HB, Betts D, Harbott J, Haas OA, Kerndrup G, Sainati L, Bergstraesser E, Hasle H, Stary J, Trebo M, van den Heuvel-Eibrink MM, Zecca M, van Wering ER, Fischer A, Noellke P, Strahm B, Locatelli F, Niemeyer CM, Schlegelberger B. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 2010;116(19):3766–9.  https://doi.org/10.1182/blood-2010-04-280313.CrossRefPubMedGoogle Scholar
  77. 77.
    Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, Head DR. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17(2):277–82.  https://doi.org/10.1038/sj.leu.2402765.CrossRefPubMedGoogle Scholar
  78. 78.
    Baumann I, Fuhrer M, Behrendt S, Campr V, Csomor J, Furlan I, de Haas V, Kerndrup G, Leguit RJ, De Paepe P, Noellke P, Niemeyer C, Schwarz S. Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria. Histopathology. 2012;61(1):10–7.  https://doi.org/10.1111/j.1365-2559.2011.04156.x.CrossRefPubMedGoogle Scholar
  79. 79.
    Forester CM, Sartain SE, Guo D, Harris MH, Weinberg OK, Fleming MD, London WB, Williams DA, Hofmann I. Pediatric aplastic anemia and refractory cytopenia: a retrospective analysis assessing outcomes and histomorphologic predictors. Am J Hematol. 2015;90(4):320–6.  https://doi.org/10.1002/ajh.23937.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Hasegawa D, Chen X, Hirabayashi S, Ishida Y, Watanabe S, Zaike Y, Tsuchida M, Masunaga A, Yoshimi A, Hama A, Kojima S, Ito M, Nakahata T, Manabe A. Clinical characteristics and treatment outcome in 65 cases with refractory cytopenia of childhood defined according to the WHO 2008 classification. Br J Haematol. 2014;166(5):758–66.  https://doi.org/10.1111/bjh.12955.CrossRefPubMedGoogle Scholar
  81. 81.
    Yoshimi A, van den Heuvel-Eibrink MM, Baumann I, Schwarz S, Simonitsch-Klupp I, de Paepe P, Campr V, Kerndrup GB, O’Sullivan M, Devito R, Leguit R, Hernandez M, Dworzak M, de Moerloose B, Stary J, Hasle H, Smith OP, Zecca M, Catala A, Schmugge M, Locatelli F, Fuhrer M, Fischer A, Guderle A, Nollke P, Strahm B, Niemeyer CM. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood. Haematologica. 2014;99(4):656–63.  https://doi.org/10.3324/haematol.2013.095786.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Yoshimi A, Niemeyer C, Baumann I, Schwarz-Furlan S, Schindler D, Ebell W, Strahm B. High incidence of Fanconi anaemia in patients with a morphological picture consistent with refractory cytopenia of childhood. Br J Haematol. 2013;160(1):109–11.  https://doi.org/10.1111/bjh.12083.CrossRefPubMedGoogle Scholar
  83. 83.
    Gohring G, Karow A, Steinemann D, Wilkens L, Lichter P, Zeidler C, Niemeyer C, Welte K, Schlegelberger B. Chromosomal aberrations in congenital bone marrow failure disorders—an early indicator for leukemogenesis? Ann Hematol. 2007;86(10):733–9.  https://doi.org/10.1007/s00277-007-0337-z.CrossRefPubMedGoogle Scholar
  84. 84.
    Ware RE, Hall SE, Rosse WF. Paroxysmal-nocturnal hemoglobinuria with onset in childhood and adolescence. N Engl J Med. 1991;325(14):991–6.  https://doi.org/10.1056/Nejm199110033251403.CrossRefPubMedGoogle Scholar
  85. 85.
    Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socie G, International PNH Interest Group. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699–709.  https://doi.org/10.1182/blood-2005-04-1717.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Shen WY, Clemente MJ, Hosono N, Yoshida K, Przychodzen B, Yoshizato T, Shiraishi Y, Miyano S, Ogawa S, Maciejewski JP, Makishima H. Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria. J Clin Invest. 2014;124(10):4529–38.  https://doi.org/10.1172/Jci74747.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Webb DK, Passmore SJ, Hann IM, Harrison G, Wheatley K, Chessells JM. Results of treatment of children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt) in Great Britain 1990-99. Br J Haematol. 2002;117(1):33–9.CrossRefPubMedGoogle Scholar
  88. 88.
    Woods WG, Barnard DR, Alonzo TA, Buckley JD, Kobrinsky N, Arthur DC, Sanders J, Neudorf S, Gold S, Lange BJ. Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children’s Cancer Group. J Clin Oncol. 2002;20(2):434–40.PubMedGoogle Scholar
  89. 89.
    Chan GC, Wang WC, Raimondi SC, Behm FG, Krance RA, Chen G, Freiberg A, Ingram L, Butler D, Head DR. Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia with a low blast count. Leukemia. 1997;11(2):206–11.CrossRefPubMedGoogle Scholar
  90. 90.
    Hasle H. Myelodysplastic and myeloproliferative disorders in children. Curr Opin Pediatr. 2007;19(1):1–8.  https://doi.org/10.1097/MOP.0b013e3280128ce8.CrossRefPubMedGoogle Scholar
  91. 91.
    Hasle H, Niemeyer CM. Advances in the prognostication and management of advanced MDS in children. Br J Haematol. 2011;154(2):185–95.  https://doi.org/10.1111/j.1365-2141.2011.08724.x.CrossRefPubMedGoogle Scholar
  92. 92.
    Pui CH, Ribeiro RC, Hancock ML, Rivera GK, Evans WE, Raimondi SC, Head DR, Behm FG, Mahmoud MH, Sandlund JT, Crist WM. Acute myeloid-leukemia in children treated with epipodophyllotoxins for acute lymphoblastic-leukemia. N Engl J Med. 1991;325(24):1682–7.  https://doi.org/10.1056/Nejm199112123252402.CrossRefPubMedGoogle Scholar
  93. 93.
    Aguilera DG, Vaklavas C, Tsimberidou AM, Wen S, Medeiros LJ, Corey SJ. Pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia: the MD Anderson Cancer Center experience. J Pediatr Hematol Oncol. 2009;31(11):803–11.CrossRefPubMedGoogle Scholar
  94. 94.
    Chu JY, Batanian JR, Gale GB, Dunphy CH, DeMello DE. Spontaneous resolution of myelodysplastic cytogenetic abnormality developed during the treatment of leukemia. J Pediatr Hematol Oncol. 1998;20(1):88–90.  https://doi.org/10.1097/00043426-199801000-00016.CrossRefPubMedGoogle Scholar
  95. 95.
    Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, Pellagatti A, Wainscoat JS, Hellstrom-Lindberg E, Gambacorti-Passerini C, Godfrey AL, Rapado I, Cvejic A, Rance R, McGee C, Ellis P, Mudie LJ, Stephens PJ, McLaren S, Massie CE, Tarpey PS, Varela I, Nik-Zainal S, Davies HR, Shlien A, Jones D, Raine K, Hinton J, Butler AP, Teague JW, Baxter EJ, Score J, Galli A, Della Porta MG, Travaglino E, Groves M, Tauro S, Munshi NC, Anderson KC, El-Naggar A, Fischer A, Mustonen V, Warren AJ, Cross NCP, Green AR, Futreal PA, Stratton MR, Campbell PJ, Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011;365(15):1384–95.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S. Frequent pathway mutations of splicing machinery in myelodysplasia. Blood. 2011;118(21):212.Google Scholar
  97. 97.
    Graubert TA, Shen D, Ding L, Okeyo-Owuor T, Lunn CL, Shao J, Krysiak K, Harris CC, Koboldt DC, Larson DE, McLellan MD, Dooling DJ, Abbott RM, Fulton RS, Schmidt H, Kalicki-Veizer J, O’Laughlin M, Grillot M, Baty J, Heath S, Frater JL, Nasim T, Link DC, Tomasson MH, Westervelt P, DiPersio JF, Mardis ER, Ley TJ, Wilson RK, Walter MJ. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet. 2012;44(1):53–U77.  https://doi.org/10.1038/ng.1031.CrossRefGoogle Scholar
  98. 98.
    Walter MJ, Shen D, Shao J, Ding L, White BS, Kandoth C, Miller CA, Niu B, McLellan MD, Dees ND, Fulton R, Elliot K, Heath S, Grillot M, Westervelt P, Link DC, DiPersio JF, Mardis E, Ley TJ, Wilson RK, Graubert TA. Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia. 2013;27(6):1275–82.  https://doi.org/10.1038/leu.2013.58.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, Schnittger S, Shiozawa Y, Kon A, Alpermann T, Yoshida K, Sanada M, Roller A, Nadarajah N, Shiraishi Y, Koeffler HP, Klein HU, Dugas M, Chiba K, Tanaka H, Kohlmann A, Miyano S, Haferlach C, Aburatani H, Kern W, Ogawa S, Haferlach T. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Blood. 2013;122(21):521.Google Scholar
  100. 100.
    Darman RB, Seiler M, Agrawal AA, Lim KH, Peng SY, Aird D, Bailey SL, Bhavsar EB, Chan B, Colla S, Corson L, Feala J, Fekkes P, Ichikawa K, Keaney GF, Lee L, Kumar P, Kunii K, MacKenzie C, Matijevic M, Mizui Y, Myint K, Park ES, Puyang XL, Selvaraj A, Thomas MP, Tsai J, Wang JY, Warmuth M, Yang H, Zhu P, Garcia-Manero G, Furman RR, Yu LH, Smith PG, Buonamici S. Cancer-associated SF3B1 hotspot mutations induce cryptic 3’ splice site selection through use of a different branch point. Cell Rep. 2015;13(5):1033–45.  https://doi.org/10.1016/j.celrep.2015.09.053.CrossRefPubMedGoogle Scholar
  101. 101.
    Malcovati L, Karimi M, Papaemmanuil E, Ambaglio I, Jadersten M, Jansson M, Elena C, Galli A, Walldin G, Della Porta MG, Raaschou-Jensen K, Travaglino E, Kallenbach K, Pietra D, Ljungstrom V, Conte S, Boveri E, Invernizzi R, Rosenquist R, Campbell PJ, Cazzola M, Lindberg EH. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood. 2015;126(2):233–41.  https://doi.org/10.1182/blood-2015-03-633537.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Visconte V, Makishima H, Jankowska A, Szpurka H, Traina F, Jerez A, O’Keefe C, Rogers HJ, Sekeres MA, Maciejewski JP, Tiu RV. SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts. Leukemia. 2012;26(3):542–5.  https://doi.org/10.1038/leu.2011.232.CrossRefPubMedGoogle Scholar
  103. 103.
    Hirabayashi S, Flotho C, Moetter J, Heuser M, Hasle H, Gruhn B, Klingebiel T, Thol F, Schlegelberger B, Baumann I, Strahm B, Stary J, Locatelli F, Zecca M, Bergstraesser E, Dworzak M, van den Heuvel-Eibrink MM, De Moerloose B, Ogawa S, Niemeyer CM, Wlodarski MW, European Working Group of MDS in Childhood. Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML. Blood. 2012;119(11):e96–9.  https://doi.org/10.1182/blood-2011-12-395087.CrossRefPubMedGoogle Scholar
  104. 104.
    Takita J, Yoshida K, Sanada M, Nishimura R, Okubo J, Motomura A, Hiwatari M, Oki K, Igarashi T, Hayashi Y, Ogawa S. Novel splicing-factor mutations in juvenile myelomonocytic leukemia. Leukemia. 2012;26(8):1879–81.  https://doi.org/10.1038/leu.2012.45.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Green CL, Tawana K, Hills RK, Bodor C, Fitzgibbon J, Inglott S, Ancliff P, Burnett AK, Linch DC, Gale RE. GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations. Br J Haematol. 2013;161(5):701–5.  https://doi.org/10.1111/bjh.12317.CrossRefPubMedGoogle Scholar
  106. 106.
    Kazenwadel J, Secker GA, Liu YJJ, Rosenfeld JA, Wildin RS, Cuellar-Rodriguez J, Hsu AP, Dyack S, Fernandez CV, Chong CE, Babic M, Bardy PG, Shimamura A, Zhang MY, Walsh T, Holland SM, Hickstein DD, Horwitz MS, Hahn CN, Scott HS, Harvey NL. Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature. Blood. 2012;119(5):1283–91.  https://doi.org/10.1182/blood-2011-08-374363.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood. 2011;118(10):2656–8.  https://doi.org/10.1182/blood-2011-06-360313.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Hahn CN, Chong CE, Carmichael CL, Wilkins EJ, Brautigan PJ, Li XC, Babic M, Lin M, Carmagnac A, Lee YK, Kok CH, Gagliardi L, Friend KL, Ekert PG, Butcher CM, Brown AL, Lewis ID, To LB, Timms AE, Storek J, Moore S, Altree M, Escher R, Bardy PG, Suthers GK, D’Andrea RJ, Horwitz MS, Scott HS. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet. 2011;43(10):1012–U130.  https://doi.org/10.1038/ng.913.CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Hsu AP, Johnson KD, Falcone EL, Sanalkumar R, Sanchez L, Hickstein DD, Cuellar-Rodriguez J, Lemieux JE, Zerbe CS, Bresnick EH, Holland SM. GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. Blood. 2013;121(19):3830–7.  https://doi.org/10.1182/blood-2012-08-452763.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Johnson KD, Hsu AP, Ryu MJ, Wang JY, Gao X, Boyer ME, Liu YG, Lee Y, Calvo KR, Keles S, Zhang J, Holland SM, Bresnick EH. Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity. J Clin Invest. 2012;122(10):3692–704.  https://doi.org/10.1172/Jci61623.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Wlodarski MW, Hirabayashi S, Pastor V, Stary J, Hasle H, Masetti R, Dworzak M, Schmugge M, van den Heuvel-Eibrink M, Ussowicz M, De Moerloose B, Catala A, Smith OP, Sedlacek P, Lankester AC, Zecca M, Bordon V, Matthes-Martin S, Abrahamsson J, Kuhl JS, Sykora KW, Albert MH, Przychodzien B, Maciejewski JP, Schwarz S, Gohring G, Schlegelberger B, Cseh A, Noellke P, Yoshimi A, Locatelli F, Baumann I, Strahm B, Niemeyer CM, EWOG-MDS. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood. 2016;127(11):1387–97.  https://doi.org/10.1182/blood-2015-09-669937.CrossRefPubMedGoogle Scholar
  112. 112.
    Rodrigues NP, Janzen V, Forkert R, Dombkowski DM, Boyd AS, Orkin SH, Enver T, Vyas P, Scadden DT. Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis. Blood. 2005;106(2):477–84.  https://doi.org/10.1182/blood-2004-08-2989.CrossRefPubMedGoogle Scholar
  113. 113.
    Ostergaard P, Simpson MA, Connell FC, Steward CG, Brice G, Woollard WJ, Dafou D, Kilo T, Smithson S, Lunt P, Murday VA, Hodgson S, Keenan R, Pilz DT, Martinez-Corral I, Makinen T, Mortimer PS, Jeffery S, Trembath RC, Mansour S. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat Genet. 2011;43(10):929–31.  https://doi.org/10.1038/ng.923.CrossRefPubMedGoogle Scholar
  114. 114.
    Pasquet M, Bellanne-Chantelot C, Tavitian S, Prade N, Beaupain B, LaRochelle O, Petit A, Rohrlich P, Ferrand C, Van den Neste E, Poirel HA, Lamy T, Ouachee-Chardin M, Mansat-De Mas V, Corre J, Recher C, Plat G, Bachelerie F, Donadieu J, Delabesse E. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood. 2013;121(5):822–9.  https://doi.org/10.1182/blood-2012-08-447367.CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Calvo KR, Vinh DC, Maric I, Wang WX, Noel P, Stetler-Stevenson M, Arthur DC, Raffeld M, Dutra A, Pak E, Myung K, Hsu AP, Hickstein DD, Pittaluga S, Holland SM. Myelodysplasia in autosomal dominant and sporadic monocytopenia immunodeficiency syndrome: diagnostic features and clinical implications. Haematologica. 2011;96(8):1221–5.  https://doi.org/10.3324/haematol.2011.041152.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Ganapathi KA, Townsley DM, Hsu AP, Arthur DC, Zerbe CS, Cuellar-Rodriguez J, Hickstein DD, Rosenzweig SD, Braylan RC, Young NS, Holland SM, Calvo KR. GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia. Blood. 2015;125(1):56–70.  https://doi.org/10.1182/blood-2014-06-580340.CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Hofmann I. Pediatric myelodysplastic syndromes. J Hematop. 2015;8(3):127–41.  https://doi.org/10.1007/s12308-015-0253-4.CrossRefGoogle Scholar
  118. 118.
    Spinner MA, Sanchez LA, Hsu AP, Shaw PA, Zerbe CS, Calvo KR, Arthur DC, Gu WJ, Gould CM, Brewer CC, Cowen EW, Freeman AF, Olivier KN, Uzel G, Zelazny AM, Daub JR, Spalding CD, Claypool RJ, Giri NK, Alter BP, Mace EM, Orange JS, Cuellar-Rodriguez J, Hickstein DD, Holland SM. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood. 2014;123(6):809–21.  https://doi.org/10.1182/blood-2013-07-515528.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Novakova M, Zaliova M, Sukova M, Wlodarski M, Janda A, Fronkova E, Campr V, Lejhancova K, Zapletal O, Pospisilova D, Cerna Z, Kuhn T, Svec P, Pelkova V, Zemanova Z, Kerndrup G, van den Heuvel-Eibrink M, van der Velden V, Niemeyer C, Kalina T, Trka J, Stary J, Hrusak O, Mejstrikova E. Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome. Haematologica. 2016;101(6):707–16.  https://doi.org/10.3324/haematol.2015.137711.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Topka S, Vijai J, Walsh MF, Jacobs L, Maria A, Villano D, Gaddam P, Wu G, RB MG, Quinn E, Inaba H, Hartford C, Pui CH, Pappo A, Edmonson M, Zhang MY, Stepensky P, Steinherz P, Schrader K, Lincoln A, Bussel J, Lipkin SM, Goldgur Y, Harit M, Stadler ZK, Mullighan C, Weintraub M, Shimamura A, Zhang J, Downing JR, Nichols KE, Offit K. Germline ETV6 mutations confer susceptibility to acute lymphoblastic leukemia and thrombocytopenia. PLoS Genet. 2015;11(6):e1005262.  https://doi.org/10.1371/journal.pgen.1005262.CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Moriyama T, Metzger ML, Wu G, Nishii R, Qian MX, Devidas M, Yang WJ, Cheng C, Cao XY, Quinn E, Raimondi S, Gastier-Foster JM, Raetz E, Larsen E, Martin PL, Bowman WP, Winick N, Komada Y, Wang SG, Edmonson M, Xu H, Mardis E, Fulton R, Pui CH, Mullighan C, Evans WE, Zhang JH, Hunger SP, Relling MV, Nichols KE, Loh ML, Yang JJ. Germline genetic variation in ETV6 and risk of childhood acute lymphoblastic leukaemia: a systematic genetic study. Lancet Oncol. 2015;16(16):1659–66.  https://doi.org/10.1016/S1470-2045(15)00369-1.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Van Vlierberghe P, Ambesi-Impiombato A, Perez-Garcia A, Haydu JE, Rigo I, Hadler M, Tosello V, Della Gatta G, Paietta E, Racevskis J, Wiernik PH, Luger SM, Rowe JM, Rue M, Ferrando AA. ETV6 mutations in early immature human T cell leukemias. J Exp Med. 2011;208(13):2571–9.  https://doi.org/10.1084/jem.20112239.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Wall M, Rayeroux KC, MacKinnon RN, Zordan A, Campbell LJ. ETV6 deletion is a common additional abnormality in patients with myelodysplastic syndromes or acute myeloid leukemia and monosomy 7. Haematologica. 2012;97(12):1933–6.  https://doi.org/10.3324/haematol.2012.069716.CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Wang Q, Dong S, Yao H, Wen L, Qiu H, Qin L, Ma L, Chen S. ETV6 mutation in a cohort of 970 patients with hematologic malignancies. Haematologica. 2014;99(10):e176–8.  https://doi.org/10.3324/haematol.2014.104406.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Churpek JE, Garcia JS, Madzo J, Jackson SA, Onel K, Godley LA. Identification and molecular characterization of a novel 3′ mutation in RUNX1 in a family with familial platelet disorder. Leuk Lymphoma. 2010;51(10):1931–5.  https://doi.org/10.3109/10428194.2010.503821.CrossRefPubMedGoogle Scholar
  126. 126.
    Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R, Loh M, Felix C, Roy DC, Busque L, Kurnit D, Willman C, Gewirtz AM, Speck NA, Bushweller JH, Li FP, Gardiner K, Poncz M, Maris JM, Gilliland DG. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999;23(2):166–75.  https://doi.org/10.1038/13793.CrossRefPubMedGoogle Scholar
  127. 127.
    Churpek JE, Lorenz R, Nedumgottil S, Onel K, Olopade OI, Sorrell A, Owen CJ, Bertuch AA, Godley LA. Proposal for the clinical detection and management of patients and their family members with familial myelodysplastic syndrome/acute leukemia predisposition syndromes. Leuk Lymphoma. 2013;54(1):28–35.  https://doi.org/10.3109/10428194.2012.701738.CrossRefPubMedGoogle Scholar
  128. 128.
    Liew E, Owen C. Familial myelodysplastic syndromes: a review of the literature. Haematologica. 2011;96(10):1536–42.  https://doi.org/10.3324/haematol.2011.043422.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Gaidzik VI, Bullinger L, Schlenk RF, Zimmermann AS, Rock J, Paschka P, Corbacioglu A, Krauter J, Schlegelberger B, Ganser A, Spath D, Kundgen A, Schmidt-Wolf IG, Gotze K, Nachbaur D, Pfreundschuh M, Horst HA, Dohner H, Dohner K. RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol. 2011;29(10):1364–72.  https://doi.org/10.1200/JCO.2010.30.7926.CrossRefPubMedGoogle Scholar
  130. 130.
    Greif PA, Konstandin NP, Metzeler KH, Herold T, Pasalic Z, Ksienzyk B, Dufour A, Schneider F, Schneider S, Kakadia PM, Braess J, Sauerland MC, Berdel WE, Buchner T, Woermann BJ, Hiddemann W, Spiekermann K, Bohlander SK. RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes. Haematologica. 2012;97(12):1909–15.  https://doi.org/10.3324/haematol.2012.064667.CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Mendler JH, Maharry K, Radmacher MD, Mrozek K, Becker H, Metzeler KH, Schwind S, Whitman SP, Khalife J, Kohlschmidt J, Nicolet D, Powell BL, Carter TH, Wetzler M, Moore JO, Kolitz JE, Baer MR, Carroll AJ, Larson RA, Caligiuri MA, Marcucci G, Bloomfield CD. RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures. J Clin Oncol. 2012;30(25):3109–18.  https://doi.org/10.1200/JCO.2011.40.6652.CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J, Alpermann T, Haferlach C, Haferlach T. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood. 2011;117(8):2348–57.  https://doi.org/10.1182/blood-2009-11-255976.CrossRefPubMedGoogle Scholar
  133. 133.
    Harada H, Harada Y, Niimi H, Kyo T, Kimura A, Inaba T. High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia. Blood. 2004;103(6):2316–24.  https://doi.org/10.1182/blood-2003-09-3074.CrossRefPubMedGoogle Scholar
  134. 134.
    Preudhomme C, Renneville A, Bourdon V, Philippe N, Roche-Lestienne C, Boissel N, Dhedin N, Andre JM, Cornillet-Lefebvre P, Baruchel A, Mozziconacci MJ, Sobol H. High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder. Blood. 2009;113(22):5583–7.  https://doi.org/10.1182/blood-2008-07-168260.CrossRefPubMedGoogle Scholar
  135. 135.
    Shiba N, Hasegawa D, Park MJ, Murata C, Sato-Otsubo A, Ogawa C, Manabe A, Arakawa H, Ogawa S, Hayashi Y. CBL mutation in chronic myelomonocytic leukemia secondary to familial platelet disorder with propensity to develop acute myeloid leukemia (FPD/AML). Blood. 2012;119(11):2612–4.  https://doi.org/10.1182/blood-2011-02-333435.CrossRefPubMedGoogle Scholar
  136. 136.
    Inoue A, Kawakami C, Takitani K, Tamai H. Azacitidine in the treatment of pediatric therapy-related myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation. J Pediatr Hematol Oncol. 2014;36(5):e322–4.  https://doi.org/10.1097/MPH.0000000000000042.CrossRefPubMedGoogle Scholar
  137. 137.
    Smith ML, Cavenagh JD, Lister TA, Fitzgibbon J. Brief report—mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004;351(23):2403–7.  https://doi.org/10.1056/NEJMoa041331.CrossRefPubMedGoogle Scholar
  138. 138.
    Tawana K, Wang J, Renneville A, Bodor C, Hills R, Loveday C, Savic A, Van Delft FW, Treleaven J, Georgiades P, Uglow E, Asou N, Uike N, Debeljak M, Jazbec J, Ancliff P, Gale R, Thomas X, Mialou V, Dohner K, Bullinger L, Mueller B, Pabst T, Stelljes M, Schlegelberger B, Wozniak E, Iqbal S, Okosun J, Araf S, Frank AK, Lauridsen FB, Porse B, Nerlov C, Owen C, Dokal I, Gribben J, Smith M, Preudhomme C, Chelala C, Cavenagh J, Fitzgibbon J. Disease evolution and outcomes in familial AML with germline CEBPA mutations. Blood. 2015;126(10):1214–23.  https://doi.org/10.1182/blood-2015-05-647172.CrossRefPubMedGoogle Scholar
  139. 139.
    Kirwan M, Walne AJ, Plagnol V, Velangi M, Ho A, Hossain U, Vulliamy T, Dokal I. Exome sequencing identifies autosomal-dominant SRP72 mutations associated with familial aplasia and myelodysplasia. Am J Hum Genet. 2012;90(5):888–92.  https://doi.org/10.1016/j.ajhg.2012.03.020.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Marquez R, Hantel A, Lorenz R, Neistadt B, Wong J, Churpek JE, Mardini NA, Shaukat I, Gurbuxani S, Miller JL, Godley LA. A new family with a germline ANKRD26 mutation and predisposition to myeloid malignancies. Leuk Lymphoma. 2014;55(12):2945–6.  https://doi.org/10.3109/10428194.2014.903476.CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Noris P, Perrotta S, Seri M, Pecci A, Gnan C, Loffredo G, Pujol-Moix N, Zecca M, Scognamiglio F, De Rocco D, Punzo F, Melazzini F, Scianguetta S, Casale M, Marconi C, Pippucci T, Amendola G, Notarangelo LD, Klersy C, Civaschi E, Balduini CL, Savoia A. Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families. Blood. 2011;117(24):6673–80.  https://doi.org/10.1182/blood-2011-02-336537.CrossRefPubMedGoogle Scholar
  142. 142.
    Pippucci T, Savoia A, Perrotta S, Pujol-Moix N, Noris P, Castegnaro G, Pecci A, Gnan C, Punzo F, Marconi C, Gherardi S, Loffredo G, De Rocco D, Scianguetta S, Barozzi S, Magini P, Bozzi V, Dezzani L, Di Stazio M, Ferraro M, Perini G, Seri M, Balduini CL. Mutations in the 5’ UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2. Am J Hum Genet. 2011;88(1):115–20.  https://doi.org/10.1016/j.ajhg.2010.12.006.CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Lewinsohn M, Brown AL, Weinel LM, Phung C, Rafidi G, Lee MK, Schreiber AW, Feng JH, Babic M, Chong CE, Lee Y, Yong A, Suthers GK, Poplawski N, Altree M, Phillips K, Jaensch L, Fine M, D’Andrea RJ, Lewis ID, Medeiros BC, Pollyea DA, King MC, Walsh T, Keel S, Shimamura A, Godley LA, Hahn CN, Churpek JE, Scott HS. Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies. Blood. 2016;127(8):1017–23.  https://doi.org/10.1182/blood-2015-10-676098.CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Li R, Sobreira N, Witmer PD, Pratz KW, Braunstein EM. Two novel germline DDX41 mutations in a family with inherited myelodysplasia/acute myeloid leukemia. Haematologica. 2016;101(6):e228–31.  https://doi.org/10.3324/haematol.2015.139790.CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Polprasert C, Schulze I, Sekeres MA, Makishima H, Przychodzen B, Hosono N, Singh J, Padgett RA, Gu X, Phillips JG, Clemente M, Parker Y, Lindner D, Dienes B, Jankowsky E, Saunthararajah Y, Du Y, Oakley K, Nguyen N, Mukherjee S, Pabst C, Godley LA, Churpek JE, Pollyea DA, Krug U, Berdel WE, Klein HU, Dugas M, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Yoshida K, Ogawa S, Muller-Tidow C, Maciejewski JP. Inherited and somatic defects in DDX41 in myeloid neoplasms. Cancer Cell. 2015;27(5):658–70.  https://doi.org/10.1016/j.ccell.2015.03.017.CrossRefPubMedGoogle Scholar
  146. 146.
    Choi JK. Hematopoietic disorders in Down syndrome. Int J Clin Exp Pathol. 2008;1(5):387–95.PubMedPubMedCentralGoogle Scholar
  147. 147.
    Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A. GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood. 2003;101(11):4301–4.  https://doi.org/10.1182/blood-2003-01-0013.CrossRefPubMedGoogle Scholar
  148. 148.
    Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet. 2002;32(1):148–52.  https://doi.org/10.1038/ng955.CrossRefPubMedGoogle Scholar
  149. 149.
    Talwalkar SS, Yin CC, Naeem RC, Hicks MJ, Strong LC, Abruzzo LV. Myelodysplastic syndromes arising in patients with germline TP53 mutation and Li-Fraumeni syndrome. Arch Pathol Lab Med. 2010;134(7):1010–5.PubMedGoogle Scholar
  150. 150.
    Link DC, Schuettpelz LG, Shen D, Wang JL, Walter MJ, Kulkarni S, Payton JE, Ivanovich J, Goodfellow PJ, Le Beau M, Koboldt DC, Dooling DJ, Fulton RS, Bender RHF, Fulton LL, Delehaunty KD, Fronick CC, Appelbaum EL, Schmidt H, Abbott R, O’Laughlin M, Chen K, McLellan MD, Varghese N, Nagarajan R, Heath S, Graubert TA, Ding L, Ley TJ, Zambetti GP, Wilson RK, Mardis ER. Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA. 2011;305(15):1568–76.  https://doi.org/10.1001/jama.2011.473.CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Alter BP. Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program. 2007;2007:29–39.  https://doi.org/10.1182/asheducation-2007.1.29.CrossRefGoogle Scholar
  152. 152.
    Tamary H, Alter BP. Current diagnosis of inherited bone marrow failure syndromes. Pediatr Hematol Oncol. 2007;24(2):87–99.  https://doi.org/10.1080/08880010601123240.CrossRefPubMedGoogle Scholar
  153. 153.
    Kee Y, D’Andrea AD. Molecular pathogenesis and clinical management of Fanconi anemia. J Clin Invest. 2012;122(11):3799–806.  https://doi.org/10.1172/JCI58321.CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol. 2013;6(3):327–37.  https://doi.org/10.1586/ehm.13.23.CrossRefPubMedGoogle Scholar
  155. 155.
    Churpek JE, Godley LA. How I diagnose and manage individuals at risk for inherited myeloid malignancies. Blood. 2016.  https://doi.org/10.1182/blood-2016-05-670240.
  156. 156.
    Parikh S, Bessler M. Recent insights into inherited bone marrow failure syndromes. Curr Opin Pediatr. 2012;24(1):23–32.  https://doi.org/10.1097/MOP.0b013e32834eca77.CrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    Kutler DI, Singh B, Satagopan J, Batish SD, Berwick M, Giampietro PF, Hanenberg H, Auerbach AD. A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood. 2003;101(4):1249–56.  https://doi.org/10.1182/blood-2002-07-2170.CrossRefPubMedGoogle Scholar
  158. 158.
    Zhang MY, Keel SB, Walsh T, Lee MK, Gulsuner S, Watts AC, Pritchard CC, Salipante SJ, Jeng MR, Hofmann I, Williams DA, Fleming MD, Abkowitz JL, King MC, Shimamura A. Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity. Haematologica. 2015;100(1):42–8.  https://doi.org/10.3324/haematol.2014.113456.CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Keel S, Scott A, Sanchez-Bonilla M, Ho PA, Gulsuner S, Pritchard CC, Abkowitz JL, King MC, Walsh T, Shimamura A. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. Haematologica. 2016;101(11):1343–50.CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Jekic B, Novakovic I, Lukovic L, Kuzmanovic M, Popovic B, Pastar I, Milasin J, Bunjevacki G, Bunjevacki V. Low frequency of NRAS and KRAS2 gene mutations in childhood myelodysplastic syndromes. Cancer Genet Cytogenet. 2004;154(2):180–2.  https://doi.org/10.1016/j.cancergencyto.2004.02.025.CrossRefPubMedGoogle Scholar
  161. 161.
    Shiba N, Kato M, Park M, Sanada M, Ito E, Fukushima K, Sako M, Arakawa H, Ogawa S, Hayashi Y. CBL mutations in juvenile myelomonocytic leukemia and pediatric myelodysplastic syndrome. Leukemia. 2010;24(5):1090–2.  https://doi.org/10.1038/leu.2010.49.CrossRefPubMedGoogle Scholar
  162. 162.
    Jekic B, Novakovic I, Lukovic L, Kuzmanovic M, Popovic B, Milasin J, Bunjevacki G, Damnjanovic T, Cvjeticanin S, Bunjevacki V. Lack of TP53 and FMS gene mutations in children with myelodysplastic syndrome. Cancer Genet Cytogenet. 2006;166(2):163–5.  https://doi.org/10.1016/j.cancergencyto.2005.11.003.CrossRefPubMedGoogle Scholar
  163. 163.
    Loyola VBP, Hirabayashi S, Pohl S, Kozyra EJ, Catala A, De Moerloose B, Dworzak M, Hasle H, Masetti R, Schmugge M, Smith O, Stary J, Ussowicz M, van den Heuvel-Eibrink MM, Mejstrikova E, Salzer U, Lubbert M, Heudobler D, Betts D, Cervera J, Gohring G, Haas OA, Haus O, Michalova K, Pasquali F, Tchinda J, van Roy N, Schlegelberger B, Beverloo HB, Noellke P, Yoshimi A, Locatelli F, Strahm B, Maciejewski JP, Rehli M, Niemeyer CM, Wlodarski MW. Somatic genetic and epigenetic architecture of myelodysplastic syndromes arising from GATA2 deficiency. Blood. 2015;126(23):299.Google Scholar
  164. 164.
    Kozyra EJ, Hirabayashi S, Loyola VBP, Przychodzen B, Karow A, Catala A, De Moerloose B, Dworzak M, Hasle H, Masetti R, Schmugge M, Smith O, Stary J, Ussowicz M, van den Heuvel-Eibrink MM, Campr V, Devito R, Paepe P, Hernandez-Marti M, Kerndrup G, Leguit R, Maldyk J, OxSullivan M, Simonitsch-Klupp I, Baumann I, Locatelli F, Maciejewski JP, Strahm B, Niemeyer CM, Wlodarski MW. Clonal mutational landscape of childhood myelodysplastic syndromes. Blood. 2015;126(23):1662.Google Scholar
  165. 165.
    Shiba N, Ohki K, Park MJ, Sotomatsu M, Kudo K, Ito E, Sako M, Arakawa H, Hayashi Y. SETBP1 mutations in juvenile myelomonocytic leukaemia and myelodysplastic syndrome but not in paediatric acute myeloid leukaemia. Br J Haematol. 2014;164(1):156–9.  https://doi.org/10.1111/bjh.12595.CrossRefPubMedGoogle Scholar
  166. 166.
    Yoshizato T, Dumitriu B, Hosokawa K, Makishima H, Yoshida K, Townsley D, Sato-Otsubo A, Sato Y, Liu D, Suzuki H, Wu CO, Shiraishi Y, Clemente MJ, Kataoka K, Shiozawa Y, Okuno Y, Chiba K, Tanaka H, Nagata Y, Katagiri T, Kon A, Sanada M, Scheinberg P, Miyano S, Maciejewski JP, Nakao S, Young NS, Ogawa S. Somatic mutations and clonal hematopoiesis in aplastic anemia. N Engl J Med. 2015;373(1):35–47.  https://doi.org/10.1056/NEJMoa1414799.CrossRefPubMedGoogle Scholar
  167. 167.
    Sasaki H, Manabe A, Kojima S, Tsuchida M, Hayashi Y, Ikuta K, Okamura J, Koike K, Ohara A, Ishii E, Komada Y, Hibi S, Nakahata T, Hematology JSP. Myelodysplastic syndrome in childhood: a retrospective study of 189 patients in Japan. Leukemia. 2001;15(11):1713–20.CrossRefPubMedGoogle Scholar
  168. 168.
    Velloso EDRP, Chauffaille ML, Pelicario LM, Tanizawa RSS, Toledo SRC, Gaiolla RD, Lopes LF. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country. Braz J Med Biol Res. 2013;46(1):85–90.  https://doi.org/10.1590/1414-431x20122449.CrossRefPubMedPubMedCentralGoogle Scholar
  169. 169.
    Kearns WG, Sutton JF, Maciejewski JP, Young NS, Liu JM. Genomic instability in bone marrow failure syndromes. Am J Hematol. 2004;76(3):220–4.  https://doi.org/10.1002/ajh.20101.CrossRefPubMedGoogle Scholar
  170. 170.
    LeBeau MM, Espinosa R, Davis EM, Eisenbart JD, Larson RA, Green ED. Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases. Blood. 1996;88(6):1930–5.Google Scholar
  171. 171.
    Wong JC, Weinfurtner KM, Alzamora MD, Kogan SC, Burgess MR, Zhang Y, Nakitandwe J, Ma J, Cheng JJ, Chen SC, Ho TT, Flach J, Reynaud D, Passegue E, Downing JR, Shannon K. Functional evidence implicating chromosome 7q22 haploinsufficiency in myelodysplastic syndrome pathogenesis. Elife. 2015\;4:e07839.  https://doi.org/10.7554/eLife.07839.CrossRefPubMedCentralGoogle Scholar
  172. 172.
    Hosono N, Makishima H, Jerez A, Yoshida K, Przychodzen B, McMahon S, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Sanada M, Gomez-Segui I, Verma AK, McDevitt MA, Sekeres MA, Ogawa S, Maciejewski JP. Recurrent genetic defects on chromosome 7q in myeloid neoplasms. Leukemia. 2014;28(6):1348–51.  https://doi.org/10.1038/leu.2014.25.CrossRefPubMedGoogle Scholar
  173. 173.
    McNerney ME, Brown CD, Wang XY, Bartom ET, Karmakar S, Bandlamudi C, Yu S, Ko JK, Sandall BP, Stricker T, Anastasi J, Grossman RL, Cunningham JM, Le Beau MM, White KP. CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood. 2013;121(6):975–83.  https://doi.org/10.1182/blood-2012-04-426965.CrossRefPubMedPubMedCentralGoogle Scholar
  174. 174.
    Chen C, Liu Y, Rappaport AR, Kitzing T, Schultz N, Zhao Z, Shroff AS, Dickins RA, Vakoc CR, Bradner JE, Stock W, LeBeau MM, Shannon KM, Kogan S, Zuber J, Lowe SW. MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia. Cancer Cell. 2014;25(5):652–65.  https://doi.org/10.1016/j.ccr.2014.03.016.CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    Lunafineman S, Shannon KM, Lange BJ. Childhood monosomy 7: epidemiology, biology, and mechanistic implications. Blood. 1995;85(8):1985–99.Google Scholar
  176. 176.
    Butcher M, Frenck R, Emperor J, Paderanga D, Maybee D, Olson K, Shannon K. Molecular evidence that childhood monosomy-7 syndrome is distinct from juvenile chronic myelogenous leukemia and other childhood myeloproliferative disorders. Genes Chromosom Cancer. 1995;12(1):50–7.  https://doi.org/10.1002/gcc.2870120109.CrossRefPubMedGoogle Scholar
  177. 177.
    Shannon KM, Turhan AG, Chang SSY, Bowcock AM, Rogers PCJ, Carroll WL, Cowan MJ, Glader BE, Eaves CJ, Eaves AC, Kan YW. Familial bone-marrow monosomy-7. Evidence that the predisposing locus is not on the long arm of chromosome-7. J Clin Invest. 1989;84(3):984–9.  https://doi.org/10.1172/Jci114262.CrossRefPubMedPubMedCentralGoogle Scholar
  178. 178.
    Sandahl JD, Coenen EA, Forestier E, Harbott J, Johansson B, Kerndrup G, Adachi S, Auvrignon A, Beverloo HB, Cayuela JM, Chilton L, Fornerod M, de Haas V, Harrison CJ, Inaba H, Kaspers GJL, Liang DC, Locatelli F, Masetti R, Perot C, Raimondi SC, Reinhardt K, Tomizawa D, von Neuhoff N, Zecca M, Zwaan CM, van den Heuvel-Eibrink MM, Hasle H. t(6;9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica. 2014;99(5):865–72.  https://doi.org/10.3324/haematol.2013.098517.CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Ahuja HG, Felix CA, Aplan PD. The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in a NUP98-TOP1 fusion. Blood. 1999;94(9):3258–61.PubMedGoogle Scholar
  180. 180.
    Gough SM, Slape CI, Aplan PD. NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights. Blood. 2011;118(24):6247–57.  https://doi.org/10.1182/blood-2011-07-328880.CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Balgobind BV, Zwaan CM, Pieters R, Van den Heuvel-Eibrink MM. The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia. Leukemia. 2011;25(8):1239–48.  https://doi.org/10.1038/leu.2011.90.CrossRefPubMedGoogle Scholar
  182. 182.
    Imamura T, Kakazu N, Hibi S, Morimoto A, Fukushima Y, Ijuin I, Hada S, Kitabayashi I, Abe T, Imashuku S. Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11). Genes Chromosom Cancer. 2003;36(4):413–9.  https://doi.org/10.1002/gcc.10172.CrossRefPubMedGoogle Scholar
  183. 183.
    Grimwade D, Freeman SD. Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for "prime time"? Blood. 2014;124(23):3345–55.  https://doi.org/10.1182/blood-2014-05-577593.CrossRefPubMedGoogle Scholar
  184. 184.
    Slap GB, Brooks JS, Schwartz JS. When to perform biopsies of enlarged peripheral lymph nodes in young patients. JAMA. 1984;252(10):1321–6.  https://doi.org/10.1001/jama.1984.03350100051031.CrossRefPubMedGoogle Scholar
  185. 185.
    Moran CA, Suster S, Abbondanzo SL. Inflammatory pseudotumor of lymph nodes: a study of 25 cases with emphasis on morphological heterogeneity. Hum Pathol. 1997;28(3):332–8.CrossRefPubMedGoogle Scholar
  186. 186.
    Jaffe ES. Histiocytoses of lymph nodes: biology and differential diagnosis. Semin Diagn Pathol. 1988;5(4):376–90.PubMedGoogle Scholar
  187. 187.
    Hemminki K, Bevier M, Hemminki A, Sundquist J. Survival in cancer of unknown primary site: population-based analysis by site and histology. Ann Oncol. 2012 Jul;23(7):1854–63.  https://doi.org/10.1093/annonc/mdr536.CrossRefPubMedGoogle Scholar
  188. 188.
    Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.  https://doi.org/10.1182/blood-2016-01-643569.CrossRefPubMedPubMedCentralGoogle Scholar
  189. 189.
    Twist CJ, Link MP. Assessment of lymphadenopathy in children. Pediatr Clin N Am. 2002;49(5):1009–25. ReviewCrossRefGoogle Scholar
  190. 190.
    Oschlies I, Burkhardt B, Salaverria I, Rosenwald A, d'Amore ES, Szczepanowski M, Koch K, Hansmann ML, Stein H, Möller P, Reiter A, Zimmermann M, Rosolen A, Siebert R, Jaffe ES, Klapper W. Clinical, pathological and genetic features of primary mediastinal large B-cell lymphomas and mediastinal gray zone lymphomas in children. Haematologica. 2011 Feb;96(2):262–8.  https://doi.org/10.3324/haematol.2010.030809.CrossRefPubMedGoogle Scholar
  191. 191.
    Young RM, Shaffer AL 3rd, Phelan JD, Staudt LM. B-cell receptor signaling in diffuse large B-cell lymphoma. Semin Hematol. 2015;52(2):77–85.  https://doi.org/10.1053/j.seminhematol.2015.01.008.CrossRefPubMedPubMedCentralGoogle Scholar
  192. 192.
    Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol. 2014;11(1):12–23.  https://doi.org/10.1038/nrclinonc.2013.197.CrossRefPubMedGoogle Scholar
  193. 193.
    Intlekofer AM, Younes A. Precision therapy for lymphoma—current state and future directions. Nat Rev Clin Oncol. 2014 Oct;11(10):585–96.  https://doi.org/10.1038/nrclinonc.2014.137.CrossRefPubMedGoogle Scholar
  194. 194.
    Liu Q, Salaverria I, Pittaluga S, Jegalian AG, Xi L, Siebert R, Raffeld M, Hewitt SM, Jaffe ES. Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma. Am J Surg Pathol. 2013;37(3):333–43.  https://doi.org/10.1097/PAS.0b013e31826b9b57.CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Salaverria I, Philipp C, Oschlies I, Kohler CW, Kreuz M, Szczepanowski M, Burkhardt B, Trautmann H, Gesk S, Andrusiewicz M, Berger H, Fey M, Harder L, Hasenclever D, Hummel M, Loeffler M, Mahn F, Martin-Guerrero I, Pellissery S, Pott C, Pfreundschuh M, Reiter A, Richter J, Rosolowski M, Schwaenen C, Stein H, Trümper L, Wessendorf S, Spang R, Küppers R, Klapper W, Siebert R, Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe, German High-Grade Lymphoma Study Group, Berlin-Frankfurt-Münster-NHL trial group. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood. 2011;118(1):139–47.  https://doi.org/10.1182/blood-2011-01-330795.CrossRefPubMedGoogle Scholar
  196. 196.
    Masqué-Soler N, Szczepanowski M, Kohler CW, Spang R, Klapper W. Molecular classification of mature aggressive B-cell lymphoma using digital multiplexed gene expression on formalin-fixed paraffin-embedded biopsy specimens. Blood. 2013;122(11):1985–6.  https://doi.org/10.1182/blood-2013-06-508937.CrossRefPubMedGoogle Scholar
  197. 197.
    Dozzo M, Carobolante F, Donisi PM, Scattolin A, Maino E, Sancetta R, Viero P, Bassan R. Burkitt lymphoma in adolescents and young adults: management challenges. Adolesc Health Med Ther. 2016;8:11–29.  https://doi.org/10.2147/AHMT.S94170.CrossRefPubMedPubMedCentralGoogle Scholar
  198. 198.
    Aiello A, Delia D, Fontanella E, Giardini R, Rilke F, Della Porta G. Expression of differentiation and adhesion molecules in sporadic Burkitt's lymphoma. Hematol Oncol. 1990;8(4):229–38.CrossRefPubMedGoogle Scholar
  199. 199.
    Love C, Sun Z, Jima D, et al. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012;44(12):1321–5.  https://doi.org/10.1038/ng.2468.CrossRefPubMedPubMedCentralGoogle Scholar
  200. 200.
    Richter J, Schlesner M, Hoffmann S, ICGC MMML-Seq Project, et al. Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nat Genet. 2012;44(12):1316–20.  https://doi.org/10.1038/ng.2469.CrossRefPubMedGoogle Scholar
  201. 201.
    Schmitz R, Young RM, Ceribelli M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490(7418):116–20.  https://doi.org/10.1038/nature11378.CrossRefPubMedPubMedCentralGoogle Scholar
  202. 202.
    Sander S, Calado DP, Srinivasan L, et al. Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis. Cancer Cell. 2012;22(2):167–79.  https://doi.org/10.1016/j.ccr.2012.06.012.CrossRefPubMedPubMedCentralGoogle Scholar
  203. 203.
    Salaverria I, Martin-Guerrero I, Wagener R, Molecular Mechanisms in Malignant Lymphoma Network Project, Berlin-Frankfurt-Münster Non-Hodgkin Lymphoma Group, et al. A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma. Blood. 2014;123(8):1187–98.  https://doi.org/10.1182/blood-2013-06-507996.CrossRefPubMedPubMedCentralGoogle Scholar
  204. 204.
    Ferreiro JF, Morscio J, Dierickx D, et al. Post-transplant molecularly defined Burkitt lymphomas are frequently MYC-negative and characterized by the 11q-gain/loss pattern. Haematologica. 2015;100(7):e275–9.  https://doi.org/10.3324/haematol.2015.124305.CrossRefPubMedPubMedCentralGoogle Scholar
  205. 205.
    Louissaint A Jr, Ackerman AM, Dias-Santagata D, et al. Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement. Blood. 2012;120(12):2395–404.  https://doi.org/10.1182/blood-2012-05-429514.CrossRefPubMedGoogle Scholar
  206. 206.
    Martin-Guerrero I, Salaverria I, Burkhardt B, et al. Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas. Haematologica. 2013;98(8):1237–41.  https://doi.org/10.3324/haematol.2012.073916.CrossRefPubMedPubMedCentralGoogle Scholar
  207. 207.
    Bruscaggin A, Monti S, Arcaini L, Ramponi A, Rattotti S, Lucioni M, Paulli M, Gaidano G, Rossi D. Molecular lesions of signalling pathway genes in clonal B-cell lymphocytosis with marginal zone features. Br J Haematol. 2014 Dec;167(5):718–20.  https://doi.org/10.1111/bjh.13052.CrossRefPubMedGoogle Scholar
  208. 208.
    Rizzo KA, Streubel B, Pittaluga S, Chott A, Xi L, Raffeld M, Jaffe ES. Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR. Mod Pathol. 2010;23(6):866–73.  https://doi.org/10.1038/modpathol.2010.63.CrossRefPubMedGoogle Scholar
  209. 209.
    Agnarsson BA, Kadin ME. Peripheral T-cell lymphomas in children. Semin Diagn Pathol. 1995;12(4):314–24.PubMedGoogle Scholar
  210. 210.
    Head DR, Kjeldsberg CR, Kadin ME, Pick T, Bybee B, Longbotham J, Shumski E. Childhood T-cell malignancy resembling adult T-cell leukemia/lymphoma. Hematol Pathol. 1987;1(1):15–25.PubMedGoogle Scholar
  211. 211.
    Perkins SL, Segal GH, Kjeldsberg CR. Work-up of lymphadenopathy in children. Semin Diagn Pathol. 1995 Nov;12(4):284–7.PubMedGoogle Scholar
  212. 212.
    Gordon BG, Weisenburger DD, Warkentin PI, et al. Peripheral T-cell lymphoma in childhood and adolescence. A clinicopathologic study of 22 patients. Cancer. 1993;71(1):257–63.CrossRefPubMedGoogle Scholar
  213. 213.
    Leake J, Kellie SJ, Pritchard J, et al. Peripheral T-cell lymphoma in childhood. A clinicopathological study of six cases. Histopathology. 1989;14(3):255–68.CrossRefPubMedGoogle Scholar
  214. 214.
    Pinkus GS, O’Hara CJ, Said JW. Peripheral/post-thymic T-cell lymphomas: a spectrum of disease. Clinical, pathologic, and immunologic features of 78 cases. Cancer. 1990;65(4):971–98.CrossRefPubMedGoogle Scholar
  215. 215.
    Lemonnier F, Couronné L, Parrens M, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120(7):1466–9.  https://doi.org/10.1182/blood-2012-02-408542.CrossRefPubMedGoogle Scholar
  216. 216.
    Sakata-Yanagimoto M, Enami T, Yoshida K, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–5.  https://doi.org/10.1038/ng.2872.CrossRefPubMedGoogle Scholar
  217. 217.
    Cairns RA, Iqbal J, Lemonnier F, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119(8):1901–3.  https://doi.org/10.1182/blood-2011-11-391748.CrossRefPubMedPubMedCentralGoogle Scholar
  218. 218.
    Nicolae A, Pittaluga S, Venkataraman G, et al. Peripheral T-cell lymphomas of follicular T-helper cell derivation with Hodgkin/Reed-Sternberg cells of B-cell lineage: both EBV-positive and EBV-negative variants exist. Am J Surg Pathol. 2013;37(6):816–26.  https://doi.org/10.1097/PAS.0b013e3182785610.CrossRefPubMedPubMedCentralGoogle Scholar
  219. 219.
    Moroch J, Copie-Bergman C, de Leval L, et al. Follicular peripheral T-cell lymphoma expands the spectrum of classical Hodgkin lymphoma mimics. Am J Surg Pathol. 2012;36(11):1636–46.  https://doi.org/10.1097/PAS.0b013e318268d9ff.CrossRefPubMedGoogle Scholar
  220. 220.
    Brugieres L, Bruneau J. Anaplastic large-cell lymphoma and peripheral T-cell lymphoma: what can pediatricians and adult oncologists learn from each other? Hematol Oncol. 2017;35(Suppl 1):70–5.  https://doi.org/10.1002/hon.2404.CrossRefPubMedGoogle Scholar
  221. 221.
    Agnarsson BA, Kadin ME. Ki-1 positive large cell lymphoma. A morphologic and immunologic study of 19 cases. Am J Surg Pathol. 1988;12(4):264–74.CrossRefPubMedGoogle Scholar
  222. 222.
    Turner SD, Lamant L, Kenner L, Brugières L. Anaplastic large cell lymphoma in paediatric and young adult patients. Br J Haematol. 2016;173(4):560–72.  https://doi.org/10.1111/bjh.13958.CrossRefPubMedGoogle Scholar
  223. 223.
    Küppers R. The biology of Hodgkin’s lymphoma. Nat Rev Cancer. 2009 Jan;9(1):15–27.  https://doi.org/10.1038/nrc2542.CrossRefPubMedGoogle Scholar
  224. 224.
    Ohno T, Stribley JA, Wu G, et al. Clonality in nodular lymphocyte- predominant Hodgkin’s disease. N Engl J Med. 1997;337(7):459–65.  https://doi.org/10.1038/nrc2542.CrossRefPubMedGoogle Scholar
  225. 225.
    Andriko JA, Aguilera NS, Nandedkar MA, et al. Childhood Hodgkin’s disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus. Mod Pathol. 1997;10(4):366–71.PubMedGoogle Scholar
  226. 226.
    Lukes RJ, Butler JJ. The pathology and nomenclature of Hodgkin’s disease. Cancer Res. 1966;26(6):1063–83.PubMedGoogle Scholar
  227. 227.
    Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84(5):1361–92.PubMedPubMedCentralGoogle Scholar
  228. 228.
    Andersson J. Epstein-Barr virus and Hodgkin’s lymphoma. Herpes. 2006;13(1):12–6.PubMedGoogle Scholar
  229. 229.
    Mason DY, Banks PM, Chan J, et al. Nodular lymphocyte predominance Hodgkin’s disease. A distinct clinicopathological entity. Am J Surg Pathol. 1994;18(5):526–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologySt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of Pathology and Laboratory MedicineLoyola University Chicago Stritch School of MedicineMaywoodUSA

Personalised recommendations