Chromosomal Translocations in AML: Detection and Prognostic Significance

Part of the Cancer Treatment and Research book series (CTAR, volume 145)


Clonal chromosome abnormalities are hallmarks of various cancer types. Non-random chromosome translocations have been identified in hematological malignancies over five decades due to their ability to yield informative metaphases. Among the various chromosome aberrations commonly found in different cancer types including deletions, duplications, and aneuploidy, balanced reciprocal translocations have been identified with remarkable specificity in hematological malignancies and soft tissue sarcomas. Recurrent chromosome aberrations are used as markers for diagnosis, prognosis, and treatment follow-up. The fusion and deregulated genes cloned from the site of translocation breakpoints are implicated in tumorigenesis. It has been well established that common molecular consequences of non-random reciprocal translocations result in the formation of a fusion gene from the breakpoints in the introns of two different genes on the same or different chromosome. Most of the fusion genes described in hematological malignancies are transcription factor genes and tyrosine kinases, conferring proliferative advantage to the leukemic clone.


Acute Myeloid Leukemia Chronic Myeloid Leukemia Acute Myeloid Leukemia Patient Translocation Breakpoint Promyelocytic Leukemia Zinc Finger 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



I thank Cancer Genetics Inc, New Jersey, USA for the inv (16) probe FISH images. This work was supported by grants from National Institutes of Health, NIH SBIR phase I grant 1R43CA091532-01 and Agency for Science Technology and Research (A-STAR) Singapore. Wilson GOH Wen Bin, for his assistance in the preparation of this article


  1. 1.
    Arrighi FE, Hsu TC. Localization of heterochromatin in human chromosomes. Cytogenetics. 1971;10:81–86.PubMedCrossRefGoogle Scholar
  2. 2.
    Becher R, Carbonell F, Bartram CR. Isochromosome 17q in Ph1-negative leukemia: a clinical, cytogenetic, and molecular study. Blood. 1990;75:1679–1683.PubMedGoogle Scholar
  3. 3.
    Berger R, Bernheim A, Daniel MT, Flandrin G. t(15;17) in a promyelocytic form of chronic myeloid leukemia blastic crisis. Cancer Genet Cytogenet. 1983;8:149–152.PubMedCrossRefGoogle Scholar
  4. 4.
    Bernard OA, Mauchauffe M, Mecucci C, Van den Berghe H, Berger R. A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Oncogene. 1994;9:1039–1045.PubMedGoogle Scholar
  5. 5.
    Bloomfield CD, Garson OM, Volin L, Knuutila S, de la Chapelle A. t(1;3)(p36;q21) in acute nonlymphocytic leukemia: a new cytogenetic-clinicopathologic association. Blood. 1985;66:1409–1413.PubMedGoogle Scholar
  6. 6.
    Borrow J, Shearman AM, Stanton VP, Jr, et al. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet. 1996;12:159–167.PubMedCrossRefGoogle Scholar
  7. 7.
    Brennan C, Zhang Y, Leo C, et al. High-resolution global profiling of genomic alterations with long oligonucleotide microarray. Cancer Res. 2004;64:4744–4748.PubMedCrossRefGoogle Scholar
  8. 8.
    Busson-Le Coniat M, Salomon-Nguyen F, Hillion J, Bernard OA, Berger R. MLL-AF1q fusion resulting from t(1;11) in acute leukemia. Leukemia. 1999;13:302–306.PubMedCrossRefGoogle Scholar
  9. 9.
    Casas S, Aventín A, Fuentes F, et al. Genetic diagnosis by comparative genomic hybridization in adult de novo acute myelocytic leukemia. Cancer Genet Cytogenet. 2004;153:16–25.PubMedCrossRefGoogle Scholar
  10. 10.
    Caspersson T, Zech L, Johansson C. Analysis of human metaphase chromosome set by aid of DNA-binding fluorescent agents. Exp Cell Res. 1970;62:490–492.PubMedCrossRefGoogle Scholar
  11. 11.
    Caligiuri MA, Strout MP, Lawrence D, et al. Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics. Cancer Res. 1998;58:55–59.PubMedGoogle Scholar
  12. 12.
    Chan WC, Carroll A, Alvarado CS, et al. Acute megakaryoblastic leukemia in infants with t(1;22)(p13;q13) abnormality. Am J Clin Pathol. 1992;98:214–221.PubMedGoogle Scholar
  13. 13.
    Claxton DF, Liu P, Hsu HB, et al. Detection of fusion transcripts generated by the inversion 16 chromosome in acute myelogenous leukemia. Blood. 1994;83:1750–1756.PubMedGoogle Scholar
  14. 14.
    de la Fuente J, Merx K, Steer EJ, et al. ABL-BCR expression does not correlate with deletions on the derivative chromosome 9 or survival in chronic myeloid leukemia. Blood. 2001;98:2879–2880.PubMedCrossRefGoogle Scholar
  15. 15.
    Dewald GW, Wyatt WA, Juneau AL, et al. Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. Blood. 1998;91:3357–3365.PubMedGoogle Scholar
  16. 16.
    Gall JG, Pardue ML. Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci USA. 1969;63:378–383.PubMedCrossRefGoogle Scholar
  17. 17.
    Garçon L, Libura M, Delabesse E, et al. DEK-CAN molecular monitoring of myeloid malignancies could aid therapeutic stratification. Leukemia. 2005;19:1338–1344.PubMedCrossRefGoogle Scholar
  18. 18.
    Goodpasture C, Bloom SE, Hsu TC, Arrighi FE. Human nucleolus organizers: the satellites or the stalks? Am J Hum Genet. 1976;28:559–566.PubMedGoogle Scholar
  19. 19.
    Grignani F, Fagioli M, Alcalay M, et al. Acute promyelocytic leukemia: from genetics to treatment. Blood. 1994;83:10–25.PubMedGoogle Scholar
  20. 20.
    Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood. 1998;92:2322–2333.PubMedGoogle Scholar
  21. 21.
    Han JY, Theil KS. The Philadelphia chromosome as a secondary abnormality in inv(3)(q21q26) acute myeloid leukemia at diagnosis: confirmation of p190 BCR-ABL mRNA by real-time quantitative polymerase chain reaction. Cancer Genet Cytogenet. 2006;165:70–74.PubMedCrossRefGoogle Scholar
  22. 22.
    Heim S, Mitelman F. Cancer Cytogenetics. New York: John Wiley & Sons, Inc; 1995.Google Scholar
  23. 23.
    Hopman AH, Wiegant J, Tesser GI, Van Duijn P. A non-radioactive in situ hybridization method based on mercurated nucleic acid probes and sulfhydryl-hapten ligands. Nucleic Acids Res. 1986;14:6471–6488.PubMedCrossRefGoogle Scholar
  24. 24.
    Hsiao HH, Sashida G, Ito Y, et al. Additional cytogenetic changes and previous genotoxic exposure predict unfavorable prognosis in myelodysplastic syndromes and acute myeloid leukemia with der(1;7)(q10;p10). Cancer Genet Cytogenet. 2006;165:161–166.PubMedCrossRefGoogle Scholar
  25. 25.
    Kang LC, Smith SV, Kaiser-Rogers K, Rao K, Dunphy CH. Two cases of acute myeloid leukemia with t(11;17) associated with varying morphology and immunophenotype: rearrangement of the MLL gene and a region proximal to the RARalpha gene. Cancer Genet Cytogenet. 2005;159:168–173.PubMedCrossRefGoogle Scholar
  26. 26.
    Klaus M, Haferlach T, Schnittger S, Kern W, Hiddemann W, Schoch C. Cytogenetic profile in de novo acute myeloid leukemia with FAB subtypes M0, M1, and M2: a study based on 652 cases analyzed with morphology, cytogenetics, and fluorescence in situ hybridization. Cancer Genet Cytogenet. 2004;155:47–56.PubMedCrossRefGoogle Scholar
  27. 27.
    Kwong YL, Liu HW, Chan LC. Racial predisposition to translocation (7;11) Leukemia. 1992;6:232.PubMedGoogle Scholar
  28. 28.
    Leroy H, de Botton S, Grardel-Duflos N, et al. Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21). Leukemia. 2005;19:367–372.PubMedCrossRefGoogle Scholar
  29. 29.
    Lin P, Medeiros LJ, Yin CC, Abruzzo LV. Translocation (3;8)(q26;q24): a recurrent chromosomal abnormality in myelodysplastic syndrome and acute myeloid leukemia. Cancer Genet Cytogenet. 2006;166:82–85.PubMedCrossRefGoogle Scholar
  30. 30.
    Mauritzson N, Albin M, Rylander L, et al. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001. Leukemia. 2002;16:2366–2378.PubMedCrossRefGoogle Scholar
  31. 31.
    Mertens F, Johansson B, Mitelman F. Isochromosomes in neoplasia. Genes Chromosomes Cancer. 1994;10:221–230.PubMedCrossRefGoogle Scholar
  32. 32.
    Mitelman F, Johansson B, Mertens F. Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat Genet. 2004;36:331–334.PubMedCrossRefGoogle Scholar
  33. 33.
    Moir DJ. A new translocation, t(1;3) (p36;q21), in myelodysplastic disorders. Blood. 1984;64:553–555.PubMedGoogle Scholar
  34. 34.
    Mrózek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev. 2004;18:115–136.PubMedCrossRefGoogle Scholar
  35. 35.
    Mrózek K, Heinonen K, de la Chapelle A, Bloomfield CD. Clinical significance of cytogenetics in acute myeloid leukemia. Semin Oncol. 1997;24:17–31.PubMedGoogle Scholar
  36. 36.
    Oshima M, Fukushima T, Koike K, Hoshida C, Izumi I, Tsuchida M. Infant leukemia with t(1;22) presenting proliferation of erythroid and megakaryocytic cell lineages. Rinsho Ketsueki. 1999;40:230–235.PubMedGoogle Scholar
  37. 37.
    Patel BB, Mohamed AN, Schiffer CA. “Acute myelogenous leukemia like” translocations in CML blast crisis: two new cases of inv(16)/t(16;16) and a review of the literature. Leuk Res. 1999;30:225–232.CrossRefGoogle Scholar
  38. 38.
    Paulsson K, Békássy AN, Olofsson T, Mitelman F, Johansson B, Panagopoulos I. A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42. Leukemia. 2006;20:224–229.PubMedCrossRefGoogle Scholar
  39. 39.
    Paulsson K, Fioretos T, Strömbeck B, Mauritzson N, Tanke HJ, Johansson B. Trisomy 8 as the sole chromosomal aberration in myelocytic malignancies: a multicolor and locus-specific fluorescence in situ hybridization study. Cancer Genet Cytogenet. 2003;140:66–69.PubMedCrossRefGoogle Scholar
  40. 40.
    Ponzetto C, Guerrasio A, Rosso C, et al. ABL proteins in Philadelphia-positive acute leukaemias and chronic myelogenous leukaemia blast crises. Br J Haematol. 1990;76:39–44.PubMedCrossRefGoogle Scholar
  41. 41.
    Potenza L, Sinigaglia B, Luppi M, et al. A t(11;20)(p15;q11) may identify a subset of nontherapy-related acute myelocytic leukemia. Cancer Genet Cytogenet. 2004;149:164–168.PubMedCrossRefGoogle Scholar
  42. 42.
    Raphael BJ, Pevzner PA. Reconstructing tumor amplisomes. Bioinformatics. 2004;20 Suppl 1:i265–i273.PubMedCrossRefGoogle Scholar
  43. 43.
    Reiter A, Walz C, Watmore A, et al. The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res. 2005;65:2662–2667.PubMedCrossRefGoogle Scholar
  44. 44.
    Rozman M, Camós M, Colomer D, et al. Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation. Genes Chromosomes Cancer. 2004;40:140–145.PubMedCrossRefGoogle Scholar
  45. 45.
    Schneider NR, Bowman WP, Frenkel EP. Translocation (3;21)(q26;q22) in secondary leukemia. Report of two cases and literature review. Ann Genet. 1991;34:256–63.PubMedGoogle Scholar
  46. 46.
    Schessl C, Rawat VP, Cusan M, et al. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest. 2005;115:2159–2168.PubMedCrossRefGoogle Scholar
  47. 47.
    Seabright M. The use of proteolytic enzymes for the mapping of structural rearrangements in the chromosomes of man. Chromosoma. 1972;36:204–210.PubMedCrossRefGoogle Scholar
  48. 48.
    Schnittger S, Kohl TM, Haferlach T, et al. KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood. 2006;107:1791–1799.PubMedCrossRefGoogle Scholar
  49. 49.
    Shimada A, Taki T, Tabuchi K, et al. KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood. 2006;107:1806–1809.PubMedCrossRefGoogle Scholar
  50. 50.
    Sierra M, Hernández JM, García JL, et al. Hematological, immunophenotypic, and cytogenetic characteristics of acute myeloblastic leukemia with trisomy 11. Cancer Genet Cytogenet. 2005;160:68–72.PubMedCrossRefGoogle Scholar
  51. 51.
    Soekarman D, von Lindern M, Daenen S, et al. The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. Blood. 1992;79:2990–2997.PubMedGoogle Scholar
  52. 52.
    Soekarman D, von Lindern M, van der Plas DC, et al. Dek-can rearrangement in translocation (6;9)(p23;q34). Leukemia. 1992;6:489–494.PubMedGoogle Scholar
  53. 53.
    Suzukawa K, Parganas E, Gajjar A, et al. Identification of a breakpoint cluster region 3’ of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI1 gene in acute myelogenous leukemias with inv(3)(q21q26). Blood. 1994;84:2681–2688.PubMedGoogle Scholar
  54. 54.
    Takatsuki H, Yufu Y, Tachikawa Y, Uike N. Monitoring minimal residual disease in patients with MLL-AF6 fusion transcript-positive acute myeloid leukemia following allogeneic bone marrow transplantation. Int J Hematol. 2002;75:298–301.PubMedCrossRefGoogle Scholar
  55. 55.
    Tanabe S, Zeleznik-Le NJ, Kobayashi H, et al. Analysis of the t(6;11)(q27;q23) in leukemia shows a consistent breakpoint in AF6 in three patients and in the ML-2 cell line. Genes Chromosomes Cancer. 1996;15:206–216.PubMedCrossRefGoogle Scholar
  56. 56.
    Thirman MJ, Levitan DA, Kobayashi H, Simon MC, Rowley JD. Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. Proc Natl Acad Sci USA. 1994;91:12110–12114.PubMedCrossRefGoogle Scholar
  57. 57.
    Tse W, Zhu W, Chen HS, Cohen A. A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells. Blood. 1995;85:650–656.PubMedGoogle Scholar
  58. 58.
    von Lindern M, Fornerod M, van Baal S, et al. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol. 1992;12:1687–1697.Google Scholar
  59. 59.
    Weltermann A, Fonatsch C, Haas OA, et al. Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse. Leukemia. 2004;18:293–302.PubMedCrossRefGoogle Scholar
  60. 60.
    Willem P, Pinto M, Bernstein R. Translocation t(1;7) revisited. Report of three further cases and review. Cancer Genet Cytogenet. 1988;36:45–54.PubMedCrossRefGoogle Scholar
  61. 61.
    Yoneda-Kato N, Look AT, Kirstein MN, et al. The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. Oncogene. 1996;18:265–275.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Pathology, Michigan Center for Translational PathologyUniversity of MichiganAnn ArborUSA

Personalised recommendations