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Acute Lymphoblastic Leukemia

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Hematologic Malignancies

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Abstract

The majority of cases of Acute Lymphoblastic Leukemia (ALL) demonstrate an abnormal karyotype, either in chromosome number (ploidy) or structural changes such as translocations, inversions or deletions, or both. The majority of cytogenetic changes are seen in B precursor ALL with only 39% occurring in T-ALL. Hyperdiploidy being the most common numerical abnormality, hypodiploid, pseudodiploid, near triploid changes are also seen. Multiple structural abnormalities including t(4;11), t(11;19), t(17;19), t(10:14), t(11;14), t(8;14) and t(12;21) as well as i(7q),i(9q),i(17q), and i(21q) are seen. Complex karyotypes are also seen in some cases.

The following case studies illustrate many of these abnormalities (Annexure).

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References

  1. Gibbons B. High hyperdiploid acute lymphoblastic leukemia. Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):145–6.

    Google Scholar 

  2. Paulsson K. High hyerdiploid childhood acute lymphoblastic leukemia: chromosomal gains as the main driver event. Mol Cell Oncol. 2016;3(1):e1064555.

    Article  Google Scholar 

  3. Raynaud, et al. Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia. Leukemia. 1999;13:1325–30.

    Article  CAS  Google Scholar 

  4. Romana SP, Poirel H, Leconiat M, et al. High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia. Blood. 1995;86(11):4263–9.

    Article  CAS  Google Scholar 

  5. Huret JL, Bernheim A. t(12;21)(p13;q22), Atlas Genet Cytogenet Oncol Haematol. 1997;1(1).

    Google Scholar 

  6. Yadav A, Bhargava M. High hypodiploidy karyotype showing t(9;22) (q34,q11.2) along with monosomy 7 in adult ALL. ASH Image Bank Published date 08/07/2018.

    Google Scholar 

  7. Heerema NA, Harbott J, Galimberti S, et al. Secondary cytogenetic aberrations in childhood, Philadelphia chromosome positive acute lymphoblastic leukemia are non random and may be associated with outcome. Leukemia. 2004;18(4):693–702.

    Article  CAS  Google Scholar 

  8. Achkar W, Wafa A, Othman M. An adult B cell precursor acute lymphoblastic leukemia with multiple secondary cytogenetic aberrations. Mol Cytogenet Published online. 2014. https://doi.org/10.1186/s13039-014-0060-0

  9. Raynaud SD, Cave H, Baens M, et al. The 12;21 translocation involving TEL and deletion of the other TEL allele: two frequently associated alterations found in childhood acute lymphoblastic leukemia. Blood. 1996 May;87(7):2891–9.

    Article  CAS  Google Scholar 

  10. Raynaud SD, Dastugue N, Zoccola D, et al. Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia. Leukemia. 1999;13:1325–30.

    Article  CAS  Google Scholar 

  11. Wafa A, Assad M, Liehr T. Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q23;p13.3)and two additional chromosome aberrations involving chromosomes 1,6,13: a case report. J Med Case Rep. 2017;11:94.

    Google Scholar 

  12. Borowitz MJ. B-lymphoblastic leukaemia/lymphoma with recurrent genetic abnormalities: WHO classification of Tumours of Haematopoietic and lymphoid tissues (revised 4th ed). IARC: Lyon; 2017.

    Google Scholar 

  13. Uckun FM, Sensel MG, Sather HN. Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children’s Cancer group. 1998;16(2)527–35.

    Google Scholar 

  14. Mohamed A. N: del (9p) in acute lymphoblastic leukemia. Atlas Genet Cytogenet Oncol Haematol. 2017;21(7):252–5.

    Google Scholar 

  15. Iacobucci I, Papayannidis C, Lonetti A. Cytogenetic and molecular predictors of outcome in acute lymphocytic leukemia: recent developments. Current Haematol Malig Rep. 2012;7:133–43.

    Article  Google Scholar 

  16. Mohamed AN. dup(1q) in ALL. Atlas Genet cytogenet Oncol Hemato. 2018;22(6):255–9.

    Google Scholar 

  17. Yamamoto K, Kawamoto S, Mizutani Y, et al. Mixed phenotype acute leukemia with t(12;17) (p13;q21) TAF15-ZNF384 and other chromosome abnormalities. Cytogenet Genome Res. 2016;149(3):165–70.

    Article  CAS  Google Scholar 

  18. Kim J, Kim HS, Choi JR. t(12;17) (p13;q12) /TAF15-ZNF 384 in acute lymphoblastic leukemia. Ann Lab Med. 2016;36(4):396–8.

    Google Scholar 

  19. Safavi S, et al. Genetic and epigenetic characterisation of hypodiploid acute lymphoblastic leukemia. Oncotarget. 2015;6:42793–802.

    Article  Google Scholar 

  20. Aldoss I, Stiller T, Cao TM, et al. The impact of additional cytogenetic abnormalities in adult with Philadelphia Chromosome-positive acute lymphoblastic leukemia undergoing allergenic hematopoietic cell transplantation. Brol Blood Marrow Transplant. 2015;21(7):1326–1329.

    Google Scholar 

  21. Achkar W, Wafa A, Othman M. An adult B cell precursor acute lymphoblastic leukemia with multiple secondary cytogenetic aberrations. Mol Cytogenet. 2014;7:60. https://doi.org/10.1186/s13039-014-0060-0.

    Article  Google Scholar 

  22. Hoelzer D, Gokbuget N. New approaches to acute lymphoblastic leukemia in adults: where do we go? Seminar Oncol. 2000;27:540–59.

    CAS  Google Scholar 

  23. Aldoss I, Stiller T, Tsai NC, et al. Therapy- related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de-novo acute lymphoblastic leukemia but outcomes are comparable in transplanted patients. Haematologica. 2018;103(10):1662–8.

    Article  Google Scholar 

  24. Ribera JM. Therapy related acute lymphoblastic leukemia haematologica. 2018;103(10):1581–3.

    Google Scholar 

  25. Neumann M, Heesch S, Gokbuget N, et al. Clinical and molecular risk subgroup in adult Characterisation of early T-cell precursor leukemia: a high of FLT3 mutations. Blood Cancer J. 2012;2:e55.

    Google Scholar 

  26. Gilliland DG, Groffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002;100:1532–42.

    Article  CAS  Google Scholar 

  27. Heerema NA, Sather HN, Sensel MG, et al. Association of chromosome 9p abnormalities with adverse risk in childhood acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood. 1999;94(5):1537–44.

    Google Scholar 

  28. Paulson K, Lilljebjor H, Biloglav A, et al. The genomic landscape of high hyerdiploid childhood acute lymphoblastic leukemia. Nat Genet. 2015;47:672–6.

    Article  Google Scholar 

  29. Paulson K. High hyperdiploid childhood acute lymphoblastic leukemia: chromosomal gains as the main driver event. Mol Cell Oncol. 2016;3(1):e1064555.

    Google Scholar 

  30. Hof J, Groeneveld-Krentz S, Schewick C, et al. Mutations and deletions of the TP53 gene predict non response to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia. J Clin Oncol. 2011; 29(23):3185–93.

    Google Scholar 

  31. Sanjuan PA, Bueno C, Prieto C, et al. Revisiting the biology of infant t(4;11)/MLL-AF4+B-cell acute lymphoblastic leukemia. Blood. 2015;126(25):2676–85.

    Article  Google Scholar 

  32. Greaves M. When one mutation is all it takes. Cancer Cell. 2015;27(4):433–4.

    Article  CAS  Google Scholar 

  33. Bardini M, Woll PS, Corral L, et al. Clonal variegation and dynamic competition of leukemia initiating cells in infant acute lymphoblastic leukemia with MLL rearrangements. Leukemia. 2015;29(1).

    Google Scholar 

  34. Raimondi SC. 11q23 rearrangements in childhood acute lymphoblastic leukemia. Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):97–102.

    Google Scholar 

  35. Safavi S, Paulson K. Near-haploid and low-hypodiploid acute lymphoblastic leukemia: two distinct subtypes with consistently poor prognosis. Blood. 2017;129(4):420–3.

    Article  CAS  Google Scholar 

  36. Wetzler M, Dodge R, Morozek K, et al. Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia. Group B Br J Haematol. 2004;124(3):275–88.

    Article  Google Scholar 

  37. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds). WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th ed). IARC: Lyon; 2017.

    Google Scholar 

  38. Kawahara Y, Iioka F, Fukutsuka K, et al. Masked Philadelphia chromosome in acute lymphoblastic leukemia. Tenri Med Bull. 2015;18(1):36–9.

    Article  Google Scholar 

  39. Huret JL. t(9,22) (q34;q11) in ALL. Atlas Gunet Cytogenet Oncol Haematol. 1997;1(1):26–8.

    Google Scholar 

  40. Yilmaz M, Kantarjian H, et al. Philadelphia chromosome positive acute lymphoblastic leukemia in adults: current treatments and future perspectives. Clin Adv Hematol Oncol. 2018;16(3).

    Google Scholar 

  41. Ravandi F, Kebriael P. Phildelphia chromosome positive acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2009;23(5).

    Google Scholar 

  42. Kantarjian HM, Talpraz M, Dhingra K. Significance of the P210 versus P 190. Molecular abnormalities in adults with Philadelphia chromosome positive acute leukemia. Blood. 1991;78:2411–8.

    Article  CAS  Google Scholar 

  43. Barber KE, Harrison CJ, Broadfield ZJ, et al. Molecular cytogenetic characterization of TCF3 (E2A/19P13.3) rearrangements B cell precursor acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2007;46(5):478–86.

    Article  CAS  Google Scholar 

  44. Tirado CA, Shabsovich D, Yeh L, et al. A t(1:29) translocation involving TCF3-PBx1 fusion within the context of a hyperdiploid karyotype in adult B-ALL: a case report and review of literature. Biomark Res. https://doi.org/10.1186/s40364-015-0029-0

  45. AL-Achkar W, Wafa A, Liehr T. An adult B-cell precursor acute lymphoblastic leukemia with multiple secondary cytogenetic aberrations. Mol Cytogenet. 2014;7:60.

    Article  Google Scholar 

  46. Zamecnikova A. i(8)(q10) on ALL. Atlas Genet Cytogenet Oncol Haematol. 2018;22(8):336–40.

    Google Scholar 

  47. Ravandi F, Kebriaei P. Philadelphia chromosome positive acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2009;23(5):1043–63.

    Article  Google Scholar 

  48. Van Der Berg E. Marian Stevens-Kroef: t(8:14) (q23:q32) / t(2;8) (p12;q24)/t(8;22) q(24;q11). Atlas Genet Cytogenes Oncol Haematol. 2017;21(2):56–9.

    Google Scholar 

  49. Abe R, Tebbi CK, Yasuda H, et al. North American Burkitt type ALL with a variant translocation t(8;22). Cancer Genet. 1982;7(3):185–95.

    Google Scholar 

  50. Ko Bor S, Tang JL, Lee FY. Additional chromosomal abnormalities and variability of BCR breakpoints in Philadelphia chromosome / BCR-ABL positive acute lymphoblastic leukemia in Taiwan. Am J Hemat. 2002;71:291–9.

    Article  Google Scholar 

  51. Walters R, Kantarjian HM, Keating MJ. The importance of cytogenetic studies in adult acute lymphoblastic leukemia. Am J Med. 1990;89:579–87.

    Article  CAS  Google Scholar 

  52. Bacher U, Haferlach T, Hiddemann W. Additional clonal abnormalities in Ph+ALL and CML demonstrate a different cytogenetic pattern at diagnosis and fellow at different pathways at progression. Cancer Genet. 2005;157(1):53–61.

    Google Scholar 

  53. Collaborative study of karyotype in childhood acute lymphoblastic leukemia. Groupe Francais de cytogenetique Hematologique. Leukemia. 1993;7(1):10–9.

    Google Scholar 

  54. Jarosova M, et al. Complex karyotypes in childhood acute lymphoblastic leukemia: cytogenetic and molecular cytogenetic study of 21 cases. Cancer Genet Cytogenetics. 2003;145(2):161–8. https://doi.org/10.1016/S0165-4608(03)00099-2.

    Article  CAS  Google Scholar 

  55. Toboso DG, Campos CB. Peripheral eosinophilia as the first manifestation of B-cell acute lymphoblastic leukemia with t(5;14) (q31;q32). Blood. 2017;130:380. https://doi.org/10.1182/blood-2016-12-754812.

    Article  CAS  PubMed  Google Scholar 

  56. Grimaldi JC, Meeker TC. The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin- 3 gene to the immunoglobulin heavy chain gene. Blood. 1989;73:2081–5. https://doi.org/10.1182/blood.V73.8.2081.2081.

    Article  CAS  PubMed  Google Scholar 

  57. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organisation classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Former Senior Advisor and Head Hematopathology, Medanta-The Medicity, New Delhi, India

    Manorama Bhargava

  2. Former Professor and Head Hematology, All India Institute of Medical Sciences and Sir Ganga Ram Hospital, New Delhi, India

    Manorama Bhargava

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  1. Manorama Bhargava
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Annexure

Annexure

  • Case Study 9.1 Acute Lymphoblastic Leukemia with High Hyperdiploidy

  • Case Study 9.2 Acute Lymphoblastic Leukemia with complex karyotype with t(12;21) (ETV6/RUNX1)

  • Case Study 9.3 Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia with Hypodiploidy, Monosomy 7, and der 6 t(2;6)

  • Case Study 9.4 Acute Lymphoblastic Leukemia with normal Karyotype with t(12;21) on FISH

  • Case Study 9.5 Acute Lymphoblastic Leukemia with t (1;19) (q23;p13.3) and i(1)(q10)

  • Case Study 9.6 Acute Lymphoblastic Leukemia with del(9p) and dup (1q)

  • Case Study 9.7 Relapsed Precursor B Acute Lymphoblastic Leukemia with t(12;17)(p13;q11.2)

  • Case Study 9.8 Philadelphia Chromosome positive Acute Lymphoblastic Leukemia with High Hypodiploidy with Monosomy 7

  • Case Study 9.9 Therapy Related Acute Lymphoblastic Leukemia with Complex Karyotype

  • Case Study 9.10 Early T Cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) with Normal Karyotype and FLT3-ITD Mutation Positive

  • Case Study 9.11 Acute Lymphoblastic Leukemia with del (9p)

  • Case Study 9.12 Acute Lymphoblastic Leukemia with High Hyperdiploidy with Complex Karyotype and TP53 Gene Deletion

  • Case Study 9.13 Acute Lymphoblastic Leukemia with Complex Karyotype with t(4;11) (q21;q23)

  • Case Study 9.14 Acute Lymphoblastic Leukemia with both Hyperdiploid and Hypodiploid Clones

  • Case Study 9.15 Philadelphia Chromosome positive acute Lymphoblastic Leukemia with additional Cytogenetic Abnormalities

  • Case Study 9.16 Acute Lymphoblastic Leukemia with masked t(9;22)

  • Case Study 9.17 Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

  • Case Study 9.18 Acute Lymphoblastic Leukemia with der 19 t(1;19) (q23;p13)

  • Case Study 9.19 Acute Lymphoblastic Leukemia with Philadelphia Chromosome t(9;22) (q34;q11.2) with i(8)(q10)and der (5) t (5;8)

  • Case Study 9.20 Acute Lymphoblastic Leukemia / non Hodgkin’s Lymphoma with a Variant t(8;22), MYC/IGL

  • Case Study 9.21 Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia with Composite Karyotype and del(7p)

  • Case Study 9.22 Acute Lymphoblastic Leukemia with Complex Karyotype

  • Case Study 9.23 Acute Lymphoblastic Leukemia with Eosinophilia

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Bhargava, M. (2021). Acute Lymphoblastic Leukemia. In: Hematologic Malignancies. Springer, Singapore. https://doi.org/10.1007/978-981-33-4799-1_9

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  • DOI: https://doi.org/10.1007/978-981-33-4799-1_9

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