Cytogenetics of MDS

  • Detlef HaaseEmail author
  • Charikleia Kelaidi
Part of the Hematologic Malignancies book series (HEMATOLOGIC)


In MDS, clonal chromosome abnormalities can be observed in 30 to >80% of patients depending on the MDS subtype and whether the disease is de novo, following an antecedent hematologic malignancy or is chemo- or radiotherapy-induced [1, 2]. In the remaining 20–70% of patients with a normal karyotype, there is a growing body of evidence that submicroscopic alterations like point mutations, microdeletions, micro amplifications, epigenetic changes or copy number neutral loss of genetic information as by uniparental disomy (UPD) constitute the genetic basis for the disease [3–5]. The cytogenetic heterogeneity in MDS is profound. In a multicentric German-Austrian study, we identified clonal karyotype changes in 1080 (52%) out of 2072 patients with MDS with a total number of 2370 clonal chromosomal abnormalities. Grouping and subdividing similar chromosomal abnormalities identified 684 different cytogenetic categories. Abnormal karyotypes showed a clear association with the severity of MDS, increasing with the medullary blast count and the intensity of cellular dysplasias [1].


  1. 1.
    Haase D, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110(13):4385–95.CrossRefPubMedGoogle Scholar
  2. 2.
    Leone G, Fianchi L, Voso MT. Therapy-related myeloid neoplasms. Curr Opin Oncol. 2011;23(6):672–80.CrossRefPubMedGoogle Scholar
  3. 3.
    Bejar R, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–506.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Boultwood J, Wainscoat JS. Gene silencing by DNA methylation in haematological malignancies. Br J Haematol. 2007;138(1):3–11.CrossRefGoogle Scholar
  5. 5.
    Mohamedali A, et al. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood. 2007;110(9):3365–73.CrossRefPubMedGoogle Scholar
  6. 6.
    Ganster C, et al. Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS. Leuk Res. 2015;39(10):1079–87. Scholar
  7. 7.
    Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, Granada I, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Valent P, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Faderl S, Pierce S, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820–9.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    McGowan-Jordan J, Simons A, Schmid M. ISCN: an international system for human cytogenetic nomenclature. Basel: Karger; 2016.Google Scholar
  9. 9.
    Pozdnyakova O, Miron P, Tang G, et al. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities. Cancer. 2008;113:3331–40.CrossRefPubMedGoogle Scholar
  10. 10.
    Solé F, Luño E, Sanzo C, et al. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica. 2005;90(9):1168–78.PubMedGoogle Scholar
  11. 11.
    Garcia-Manero G. Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification and management. Am J Hematol. 2014;89(1):97–108.CrossRefPubMedGoogle Scholar
  12. 12.
    Malcovati L, Cazzola M. The shadowlands of MDS: idiopathic cytopenias of undetermined significance (ICUS) and clonal hematopoiesis of indeterminate potential (CHIP). Hematology Am Soc Hematol Educ Program. 2015;2015:299–307.PubMedGoogle Scholar
  13. 13.
    Malcovati L, Hellström-Lindberg E, Bowen D, et al. European Leukemia Net. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943–64.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    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. Scholar
  16. 16.
    Valcárcel D, Ademà V, Solé F, Ortega M, Nomdedeu B, Sanz G, Luño E, Cañizo C, de la Serna J, Ardanaz M, Marco V, Collado R, Grau J, Montoro J, Mallo M, Vallespí T. Complex, not monosomal, karyotype is the cytogenetic marker of poorest prognosis in patients with primary myelodysplastic syndrome. J Clin Oncol. 2013;31(7):916–22. Scholar
  17. 17.
    Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51. Scholar
  18. 18.
    Fenaux P, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Haferlach C, et al. Proposals for standardized protocols for cytogenetic analyses of acute leukemias, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloprolifera-tive disorders, and myelodysplastic syndromes. Genes Chromosomes Cancer. 2007;46(5):494–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennet J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Della Porta MG, Malcovati L, Boveri E, Travaglino E, Pietra D, Pascutto C, Passamonti F, Invernizzi R, Castello A, Magrini U, Lazzarino M, Cazzola M. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol. 2009;27(5):754–62. Scholar
  23. 23.
    Tong WG, Quintás-Cardama A, Kadia T, Borthakur G, Jabbour E, Ravandi F, Faderl S, Wierda W, Pierce S, Shan J, Bueso-Ramos C, Kantarjian H, Garcia-Manero G. Predicting survival of patients with hypocellular myelodysplastic syndrome: development of a disease specific prognostic score system. Cancer. 2012;118(18):4462–70. Scholar
  24. 24.
    Jabbour E, Takahashi K, Wang X, Megan Cornelison A, Abruzzo L, Kadia T, Borthakur G, Estrov Z, O’Brien S, Mallo M, Wierda W, Pierce S, Wei Y, Sole F, Chen R, Kantarjian H, Garcia-Manero G. Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia. Am J Hematol. 2013;88(10):831–7.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Giagounidis A, Haase D. Morphology, cytogenetics and classification of MDS. Best Pract Res Clin Haematol. 2013;26(4):337–53. Scholar
  26. 26.
    Ohyashiki JH, Ohyashiki K, Fujimura T, Kawakubo K, Shimamoto T, Iwabuchi A, Toyama K. Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes. Cancer Res. 1994;54:3557–60.PubMedGoogle Scholar
  27. 27.
    Braulke F, et al. Molecular cytogenetic monitoring from CD34+ peripheral blood cells in myelodysplastic syndromes: first results from a prospective multicenter German diagnostic study. Leuk Res. 2013;37(8):900–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Platzbecker U, et al. Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study. Leukemia. 2013;27(6):1403–7. Scholar
  29. 29.
    de Oliveira FM, Miguel CE, Lucena-Araujo AR, de Lima AS, Falcão RP, Rego EM. FISH analysis for TET2 deletion in a cohort of 362 Brazilian myeloid malignancies: correlation with karyotype abnormalities. Med Oncol. 2013;30(1):483.CrossRefPubMedGoogle Scholar
  30. 30.
    Ademà V, Hernández JM, Abáigar M, Lumbreras E, Such E, Calull A, Dominguez E, Arenillas L, Mallo M, Cervera J, Marugán I, Tormo M, García F, González T, Luño E, Sanzo C, Martín ML, Fernández M, Costa D, Blázquez B, Barreña B, Marco F, Batlle A, Buño I, Martínez-Laperche C, Noriega V, Collado R, Ivars D, Carbonell F, Vallcorba I, Melero J, Delgado E, Vargas MT, Grau J, Salido M, Espinet B, Melero C, Florensa L, Pedro C, Solé F. Application of FISH 7q in MDS patients without monosomy 7 or 7q deletion by conventional G-banding cytogenetics: does -7/7q- detection by FISH have prognostic value? Leuk Res. 2013;37(4):416–21. Scholar
  31. 31.
    Lai YY, Huang XJ, Li J, Zou P, Xu ZF, Sun H, Shao ZH, Zhou DB, Chen FP, Liu ZG, Zhu HL, Wu DP, Wang C, Zhang Y, Li Y, Hou M, Du X, Wang X, Li W, Lai YR, Zhou J, Zhou YH, Fang MY, Qiu L, Wang XM, Zhang GS, Jiang M, Liang YM, Zhang LS, Chen XQ, Bai H, Lin JY. Standardized fluorescence in situ hybridization testing based on an appropriate panel of probes more effectively identifies common cytogenetic abnormalities in myelodysplastic syndromes than conventional cytogenetic analysis: a multicenter prospective study of 2302 patients in China. Leuk Res. 2015;39(5):530–5. Scholar
  32. 32.
    Mallo M, Arenillas L, Espinet B, Salido M, Hernández JM, Lumbreras E, del Rey M, Arranz E, Ramiro S, Font P, González O, Renedo M, Cervera J, Such E, Sanz GF, Luño E, Sanzo C, González M, Calasanz MJ, Mayans J, García-Ballesteros C, Amigo V, Collado R, Oliver I, Carbonell F, Bureo E, Insunza A, Yañez L, Muruzabal MJ, Gómez-Beltrán E, Andreu R, León P, Gómez V, Sanz A, Casasola N, Moreno E, Alegre A, Martín ML, Pedro C, Serrano S, Florensa L, Solé F. Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q. Haematologica. 2008;93(7):1001–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Mallo MDM, Cervera J, Schanz J, Espinet B, Such E, Luno E, Steidl C, Martin ML, Germing U, Grau J, Pfeilstoecker M, Hernandez JM, Noesslinger T, Calasanz MJ, Valent P, Collado R, Fonatsch C, Bureo E, Lübbert M, Rios R, Stauder R, Arranz E, Hildebrandt B, Slovak ML, Ciguidosa J, Eclache V, Krieger O, Pedro C, Salido M, Arenillas L, Sanz G, Sanz MA, Valencia A, Florensa L, Haase D, Solé F. Prognostic impact of additional chromosomal aberrations (ACA) to 5q-in patients with primary myelodysplastic syndrome. Blood. 2008;112:582.Google Scholar
  34. 34.
    Braulke F, Müller-Thomas C, Götze K, Platzbecker U, Germing U, Hofmann WK, Giagounidis AA, Lübbert M, Greenberg PL, Bennett JM, Solé F, Slovak ML, Ohyashiki K, Le Beau MM, Tüchler H, Pfeilstöcker M, Hildebrandt B, Aul C, Stauder R, Valent P, Fonatsch C, Bacher U, Trümper L, Haase D, Schanz J. Frequency of del(12p) is commonly underestimated in myelodysplastic syndromes: results from a German diagnostic study in comparison with an international control group. Genes Chromosomes Cancer. 2015;54(12):809–17. Scholar
  35. 35.
    Braulke F, Platzbecker U, Müller-Thomas C, Götze K, Germing U, Brümmendorf TH, Nolte F, Hofmann WK, Giagounidis AA, Lübbert M, Greenberg PL, Bennett JM, Solé F, Mallo M, Slovak ML, Ohyashiki K, Le Beau MM, Tüchler H, Pfeilstöcker M, Nösslinger T, Hildebrandt B, Shirneshan K, Aul C, Stauder R, Sperr WR, Valent P, Fonatsch C, Trümper L, Haase D, Schanz J. Validation of cytogenetic risk groups according to international prognostic scoring systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group. Haematologica. 2015;100(2):205–13.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Cherry AM, Slovak ML, Campbell LJ, Chun K, Eclache V, Haase D, Haferlach C, Hildebrandt B, Iqbal AM, Jhanwar SC, Ohyashiki K, Sole F, Vandenberghe P, VanDyke DL, Zhang Y, Dewald GW. Will a peripheral blood (PB) sample yield the same diagnostic and prognostic cytogenetic data as the concomitant bone marrow (BM) in myelodysplasia? Leuk Res. 2012;36(7):832–40.CrossRefPubMedGoogle Scholar
  37. 37.
    Coleman JF, Theil KS, Tubbs RR, Cook JR. Diagnostic yield of bone marrow and peripheral blood FISH panel testing in clinically suspected myelodysplastic syndromes and/or acute myeloid leukemia: a prospective analysis of 433 cases. Am J Clin Pathol. 2011;135(6):915–20.CrossRefPubMedGoogle Scholar
  38. 38.
    Costa D, Valera S, Carrió A, Arias A, Muñoz C, Rozman M, et al. Do we need to do fluorescence in situ hybridization analysis in myelodysplastic syndromes as often as we do? Leuk Res. 2010;34:1437–41.CrossRefPubMedGoogle Scholar
  39. 39.
    Jiang H, Xue Y, Wand Q, Pan J, Wu Y, Zhang J, et al. The utility of fluorescence in situ hybridization analysis in diagnosing myelodysplastic syndromes is limited to cases with karyotype failure. Leuk Res. 2012;36:448–52.CrossRefPubMedGoogle Scholar
  40. 40.
    Kwon WK, Lee JY, Mun YC, Seong CM, Chung WS, Huh J. Clinical utility of FISH analysis in adition to G-banded karyotype in hematologic malignancies and proposal of practical research. Korean J Hematol. 2010;45:171–6.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Pinheiro RF, Chauffaille MLLF. Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities during the evolution of myelodysplastic syndrome. Braz J Med Biol Res. 2009;42:1110–2.CrossRefPubMedGoogle Scholar
  42. 42.
    Pitchford CW, Hettinga AC, Reichard KK. Fluorescence in situ hybridization testing for -5/5q-, -7/7q-, +8, and del(20q) in primary myelodysplastic syndrome correlates with conventional cytogenetics in the setting of an adequate study. Am J Clin Pathol. 2010;133:260–4.CrossRefPubMedGoogle Scholar
  43. 43.
    Vehmeyer K, Haase D, Alves F. Increased peripheral stem cell pool in MDS: an indication of disease progression? Leuk Res. 2001;25:955–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Haase D, Feuring-Buske M, Könemann S, Fonatsch C, Troff C, Verbeek W, Pekrun A, Hiddemann W, Wörmann B. Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations. Blood. 1995;86(8):2906–12.PubMedGoogle Scholar
  45. 45.
    Haase D, Feuring-Buske M, Schäfer C, Schoch C, Troff C, Gahn B, Hiddemann W, Wörmann B. Cytogenetic analysis of CD34+ subpopulations in AML and MDS characterized by the expression of CD38 and CD117. Leukemia. 1997;11:674–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Braulke F, Schanz J, Jung K, Shirneshan K, Schulte K, Schuetze C, Steffens R, Truemper L, Haase D. FISH analysis of circulating CD34+ cells as a new tool for genetic monitoring in MDS: verification of the method and application to 27 MDS patients. Leuk Res. 2010;34(10):1296–301. Scholar
  47. 47.
    Schuler E, Giagounidis A, Haase D, Shirneshan K, Büsche G, Platzbecker U, et al. Results of a multicenter prospective phase II trial investigating the safety and efficacy of lenalidomide in patients with myelodysplastic syndromes with isolated del(5q) (LE-MON 5). Leukemia. 2015;30(7):1580.CrossRefPubMedGoogle Scholar
  48. 48.
    Bernasconi P, Klersy C, Boni M, Cavigliano PM, Giardini I, Rocca B, Zappatore R, Dambruoso I, Calvello C, Caresana M, Lazzarino M. Does cytogenetic evolution have any prognostic relevance in myelodysplastic syndromes? A study on 153 patients from a single institution. Ann Hematol. 2010;89(6):545–51. Scholar
  49. 49.
    Tricot G, Boogaerts MA, De Wolf-Peeters C, Van den Berghe H, Verwilghen RL. The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations. Br J Haematol. 1985;59:659–70.CrossRefPubMedGoogle Scholar
  50. 50.
    Haferlach C, Zenger M, Alpermann T, Schnittger S, Kern W, Haferlach T. Cytogenetic clonal evolution in MDS is associated with shifts towards unfavorable karyotypes according to IPSS and shorter overall survival: a study on 988 MDS patients studied sequentially by chromosome banding analysis. Blood. 2011;118:968.Google Scholar
  51. 51.
    Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144(1):27–40. Scholar
  52. 52.
    Trost D, Hildebrandt B, Beier M, Müller N, Germing U, Royer-Pokora B. Molecular cytogenetic profiling of complex karyotypes in primary myelodysplastic syndromes and acute myeloid leukemia. Cancer Genet Cytogenet. 2006;165:51–63.CrossRefPubMedGoogle Scholar
  53. 53.
    Schoch C, Kern W, Kohlmann A, Hiddemann W, Schnittger S, Haferlach T. Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological entity characterized by genomic imbalances and a specific gene expression profile. Genes Chromosomes Cancer. 2005;43:227–38.CrossRefPubMedGoogle Scholar
  54. 54.
    Kulasekararaj AG, Smith AE, Mian SA, et al. TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haematol. 2013;160(5):660–72.CrossRefPubMedGoogle Scholar
  55. 55.
    Volkert S, Kohlmann A, Schnittger S, et al. Association of the type of 5q loss with complex karyotype, clonal evolution, TP53 mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome. Genes Chromosomes Cancer. 2014;53(5):402–10.CrossRefPubMedGoogle Scholar
  56. 56.
    Schaab R, Ganster C, Dierks S, Shirneshan K, Parra MT, Martin R, Germing U, Platzbecker U, Lange F, Kroeger N, Döhner K, Glass B, Nickelsen M, Stuhlmann R, Truemper LH, Schanz J, Bacher U, Haase D. Interdependency between TP53 mutations, cytogenetics, genetic Instability and prognosis in MDS and secondary AML. Blood. 2016;128:22.Google Scholar
  57. 57.
    Rücker FG, Bullinger L, Schwaenen C, Lipka DB, Wessendorf S, Frohling S, Bentz M, Miller S, Scholl C, Schlenk RF, Radlwimmer B, Kestler HA, Pollack JR, Lichter P, Döhner K, Döhner H. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol. 2006;24:3887–94.CrossRefPubMedGoogle Scholar
  58. 58.
    Schanz J, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Tuechler H, Valent P, Hildebrandt B, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Kantarjian H, Germing U, Haase D, Estey E. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the international prognostic scoring system. J Clin Oncol. 2011;29(15):1963–70.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK, National 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. Scholar
  60. 60.
    Boultwood J, Wainscoat JS. Clonality in the myelodysplastic syndromes. Int J Hematol. 2001;73:411–5.CrossRefPubMedGoogle Scholar
  61. 61.
    Cermák J, Belicková M, Krejcová H, Michalová K, Zilovcová S, Zemanová Z, Brezinová J, Sieglová Z. The presence of clonal cell subpopulations in peripheral blood and bone marrow of patients with refractory cytopenia with multilineage dysplasia but not in patients with refractory anemia may reflect a multistep pathogenesis of myelodysplasia. Leuk Res. 2005;29:371–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Galili N, Cerny J, Raza A. Current treatment options: impact of cytogenetics on the course of myelodysplasia. Curr Treat Options Oncol. 2007;8:117–28.CrossRefPubMedGoogle Scholar
  63. 63.
    Nilsson L, Astrand-Grundström I, Anderson K, Arvidsson I, Hokland P, Bryder D, Kjeldsen L, Johansson B, Hellström-Lindberg E, Hast R, Jacobsen SEW. Involvement and functional impairment of the CD34+CD38-Thy-1+ hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood. 2002;100:259–67.PubMedGoogle Scholar
  64. 64.
    Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K, Larson DE, McLellan MD, Dooling D, Abbott R, Fulton R, Magrini V, Schmidt H, Kalicki-Veizer J, O’Laughlin M, Fan X, Grillot M, Witowski S, Heath S, Frater JL, Eades W, Tomasson M, Westervelt P, DiPersio JF, Link DC, Mardis ER, Ley TJ, Wilson RK, Graubert TA. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med. 2012;366(12):1090–8.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Johansson B, Mertens F, Mitelman F. Primary vs, secondary neoplasia-associated chromosomal abnormalities - balanced rearrangements vs, genomic imbalances? Genes Chromosomes Cancer. 1996;16:155–63.CrossRefPubMedGoogle Scholar
  66. 66.
    Mitelman F. Catalog of chromosome aberrations in cancer. 6th ed. New York: Wiley-Liss; 1998.Google Scholar
  67. 67.
    Steidl C, Schabla R, Germing U, Hildebrandt B, Noesslinger T, Pfeilstoecker M, Giagounidis A, Kunzmann R, Haas P, Luebbert M, Truemper L, Haase D. Sequential cytogenetic analyses of 577 patients with myelodysplastic syndromes: Correlations between initial karyotype, cytogenetic dynamics, and clinical course. Blood. 2005;106:2531.Google Scholar
  68. 68.
    Lai YY, Qiu JY, Zhang Y, Shi Y, He Q, Dang H, Lu DP. Clinical significance of continuous karyotyping in myelodysplastic syndromes. Zhonghua Xue Ye Xue Za Zhi. 2004;25:645–8.PubMedGoogle Scholar
  69. 69.
    Tien HF, Wang CH, Chuang SM, Lee FY, Liu MC, Chen YC, Shen MC, Lin KH, Lin DT. Acute leukemic transformation of myelodysplastic syndrome – immunophenotypic, genotypic, and cytogenetic studies. Leuk Res. 1995;19:595–603.CrossRefPubMedGoogle Scholar
  70. 70.
    White NJ, Nacheva E, Asimakopoulos FA, Bloxham D, Paul B, Green AR. Deletion of chromosome 20q in myelodysplasia can occur in a multipotent precursor of both myeloid cells and B-cells. Blood. 1994;83:2809–16.PubMedGoogle Scholar
  71. 71.
    Ghaddar HM, Stass SA, Pierce S, Estey EH. Cytogenetic evolution following the transformation of myelodysplastic syndrome to acute myelogenous leukemia: implications on the overlap between the two diseases. Leukemia. 1994;8:1649–53.PubMedGoogle Scholar
  72. 72.
    Horiike S, Taniwaki M, Misawa S, Abe T. Chromosome abnormalities and karyotypic evolution in 83 patients with myelodysplastic syndrome and predictive value for prognosis. Cancer. 1988;62:1129–38.CrossRefPubMedGoogle Scholar
  73. 73.
    Horiike S, Misawa S, Nakai H, Kaneko H, Yokota S, Taniwaki M, Yamane Y, Inazawa J, Abe T, Kashima K. N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndromes. Leukemia. 1994;8:1331–6.PubMedGoogle Scholar
  74. 74.
    Daniel CP, Ponting IL, Dexter TM. Growth and development of haemopoietic cells: a deterministic process? Haematol Blood Transfus. 1989;32:172–7.PubMedGoogle Scholar
  75. 75.
    Kanamaru A, Tamura S. Application of long-term marrow cultures for studying the leukemic transformation of myelodysplastic syndromes. Leuk Lymphoma. 1993;11:345–52.CrossRefPubMedGoogle Scholar
  76. 76.
    Tamura S, Kanamaru A, Takemoto Y, Kakishita E, Nagai K. Clonal evolutions during long-term cultures of bone marrow from de novo acute myeloid leukemia with trilineage myelodysplasia and with myelodysplastic remission marrow. Br J Haematol. 1993;84:219–26.CrossRefPubMedGoogle Scholar
  77. 77.
    Michalová K, Cermák J, Brezinová J, Zemanová Z. Double minute chromosomes in a patient with myelodysplastic syndrome transforming into acute myeloid leukemia. Cancer Genet Cytogenet. 1999;109:76–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Reddy KS, Sulcova V. c-myc amplification in a preleukemia patient with trisomy 4 and double minutes: Review of the unique coexistence of these two chromosome abnormalities in acute myelogenous leukemia. Cancer Genet Cytogenet. 1997;95:206–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Pinheiro RF, de Sá Moreira ED, Silva MRR, Alberto FL, Chauffaille M. FLT3 internal tandem duplication during myelodysplastic syndrome follow-up: a marker of transformation to acute myeloid leukemia. Cancer Genet Cytogenet. 2008;183:89–93.CrossRefPubMedGoogle Scholar
  80. 80.
    Lorenzo F, Nishii K, Mortma F, Kuwagata S, Usui E, Shiku H. Mutational analysis of the KIT gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. Leuk Res. 2006;30:1235–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Mori N, Morosetti R, Hoflehner E, Lübbert M, Mizoguchi H, Koeffler HP. Allelic loss in the progression of myelodysplastic syndrome. Cancer Res. 2000;60:3039–42.PubMedGoogle Scholar
  82. 82.
    Harada S, Komatsu H, Seto M, Ni HP, Xu JH, Hayami Y, Tsuboi K, Wakita A, Nitta M, Kato T, Ueda R. Microsatellite instability is rare in the clinical course of myelodysplastic syndrome studied with DNA from fresh and paraffin embedded tissues. J Cancer Res Clin Oncol. 1998;124:231–5.CrossRefPubMedGoogle Scholar
  83. 83.
    Maeck L, Haase D, Schoch C, Hiddemann W, Alves F. Genetic instability in myelodysplastic syndrome: detection of microsatellite instability and loss of heterozygosity in bone marrow samples with karyotype alterations. Br J Haematol. 2000;109:842–6.CrossRefPubMedGoogle Scholar
  84. 84.
    Tasaka T, Lee S, Spira S, Takeuchi S, Hatta Y, Nagai M, Takahara J, Koeffler HP. Infrequent microsatellite instability during the evolution of the myelodysplastic syndrome to acute myelocytic leukemia. Leuk Res. 1996;20:113–7.CrossRefGoogle Scholar
  85. 85.
    Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D. Myelodysplastic syndromes: A scoring system with prognostic significance. Br J Haematol. 1985;59(3):425–33.CrossRefPubMedGoogle Scholar
  86. 86.
    Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S, Irriguible D, San Miguel JF. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: A multivariate analysis of prognostic factors in 370 patients. Blood. 1989;74(1):395–408.PubMedGoogle Scholar
  87. 87.
    Morel P, Hebbar M, Lai JL, Duhamel A, Preudhomme C, Wattel E, Bauters F, Fenaux P. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia. 1993;7(9):1315–23.PubMedGoogle Scholar
  88. 88.
    Bernasconi P, Klersy C, Boni M, Cavigliano PM, Dambruoso I, Zappatore R. Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution. Am J Hematol. 2013;88(2):120–9.CrossRefPubMedGoogle Scholar
  89. 89.
    Voso MT, Fenu S, Latagliata R, Buccisano F, Piciocchi A, Aloe-Spiriti MA, Venditti A. Revised international prognostic scoring system (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO prognostic scoring system: Validation by the Gruppo Romano Mielodisplasie Italian regional database. J Clin Oncol. 2013;31(21):2671–7.CrossRefPubMedGoogle Scholar
  90. 90.
    Itzykson R, Thépot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Salanoubat C, Visanica S, Stamatoullas A, Isnard F, Marfaing-Koka A, de Botton S, Chelghoum Y, Taksin AL, Plantier I, Ame S, Boehrer S, Gardin C, Beach CL, Adès L, Fenaux P, Groupe Francophone des Myelodysplasies (GFM). Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403–11.CrossRefPubMedGoogle Scholar
  91. 91.
    Lamarque M, Raynaud S, Itzykson R, Thepot S, Quesnel B, Dreyfus F, Rauzy OB, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Visanica S, Stamatoullas A, Fenaux P, Adès L. The revised IPSS is a powerful tool to evaluate the outcome of MDS patients treated with azacitidine: the GFM experience. Blood. 2012;120(25):5084–5.CrossRefPubMedGoogle Scholar
  92. 92.
    de Witte T, Bowen D, Robin M, Malcovati L, Niederwieser D, Yakoub-Agha I, Mufti GJ, Fenaux P, Sanz G, Martino R, Alessandrino EP, Onida F, Symeonidis A, Passweg J, Kobbe G, Ganser A, Platzbecker U, Finke J, van Gelder M, van de Loosdrecht AA, Ljungman P, Stauder R, Volin L, Deeg HJ, Cutler C, Saber W, Champlin R, Giralt S, Anasetti C, Kröger N. Use of hematopoietic cell transplantation for patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2017;130:92.Google Scholar
  93. 93.
    Gerds AT, Gooley TA, Wilson WA, Deeg HJ. Components of the revised international prognostic scoring system and outcome after hematopoietic cell transplantation for myelodysplastic syndrome. Blood. 2013;121(19):4007–8.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Mishra A, Corrales-Yepez M, Ali NA, Kharfan-Dabaja M, Padron E, Zhang L, Epling-Burnette PK, Pinilla-Ibarz J, Lancet JE, List AF, Komrokji RS. Validation of the revised international prognostic scoring system in treated patients with myelodysplastic syndromes. Am J Hematol. 2013;88(7):566–70.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, Giagounidis A, Hildebrandt B, Bernasconi P, Knipp S, Strupp C, Lazzarino M, Aul C, Cazzola M. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25(23):3503–10.CrossRefPubMedGoogle Scholar
  96. 96.
    Malcovati L, Della Porta MG, Strupp C, Ambaglio I, Kuendgen A, Nachtkamp K, Travaglino E, Invernizzi R, Pascutto C, Lazzarino M, Germing U, Cazzola M. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based prognostic scoring system (WPSS). Haematologica. 2011;96(10):1433–40.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Della Porta MG, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres MA, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D, Greenberg PL, Cazzola M. Validation of WHO classification-based prognostic scoring system (WPSS) for myelodysplastic syndromes and comparison with the revised international prognostic scoring system (IPSS-R). A study of the international working group for prognosis in myelodysplasia (IWG-PM). Leukemia. 2015;29(7):1502–13.CrossRefPubMedGoogle Scholar
  98. 98.
    Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, Wierda WG, Pierce S, Estey E, Liu J, Huang X, Kantarjian H. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22(3):538–43.CrossRefPubMedGoogle Scholar
  99. 99.
    Kantarjian H, O’Brien S, Ravandi F, Cortes J, Shan J, Bennett JM, Garcia-Manero G. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original international prognostic scoring system. Cancer. 2008;113(6):1351–61.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Such E, Cervera J, Costa D, Solé F, Vallespí T, Luño E, Collado R, Calasanz MJ, Hernández-Rivas JM, Cigudosa JC, Nomdedeu B, Mallo M, Carbonell F, Bueno J, Ardanaz MT, Ramos F, Tormo M, Sancho-Tello R, del Cañizo C, Gómez V, Marco V, Xicoy B, Bonanad S, Pedro C, Bernal T, Sanz GF. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica. 2011;96(3):375–83.CrossRefPubMedGoogle Scholar
  101. 101.
    Such E, Germing U, Malcovati L, Cervera J, Kuendgen A, Della Porta MG, Nomdedeu B, Arenillas L, Luño E, Xicoy B, Amigo ML, Valcarcel D, Nachtkamp K, Ambaglio I, Hildebrandt B, Lorenzo I, Cazzola M, Sanz G. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood. 2013;121(15):3005–15.CrossRefPubMedGoogle Scholar
  102. 102.
    Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, Grau J, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Valent P, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D. Monosomal karyotype in MDS: explaining the poor prognosis? Leukemia. 2013;27(10):1988–95.CrossRefPubMedGoogle Scholar
  103. 103.
    Pfeilstöcker M, Tuechler H, Sanz G, Schanz J, Garcia-Manero G, Solé F, Greenberg PL. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016;128(7):902–10.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinics of Hematology and Medical OncologyUniversity Medical Center GöttingenGöttingenGermany
  2. 2.Department of Pediatric Hematology and Oncology“Aghia Sophia” Children’s HospitalAthensGreece

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