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Gene Translocations and Deletions in Myeloid Malignancies

Translocation t(2;3)(p15–23;q26–27) in myeloid malignancies: report of 21 new cases, clinical, cytogenetic and molecular genetic features

Leukemia volume 18, pages 1108–1114 (2004)Cite this article

Abstract

Chromosomal rearrangements involving 3q26 either due to inversion or translocation with various partner chromosomes are a recurrent finding in malignant myeloid disorders. Typically, these chromosome aberrations contribute to ectopic expression of or to the formation of fusion genes involving the EVI1 proto-oncogene. Chromosomal translocations involving the short arm of chromosome 2 (p15–p23) and the distal part of the long arm of chromosome 3 (q26–q27) are a rare but recurrent finding in patients with myeloid malignancies, and are assumed to be part of this spectrum of disorders. Thus far, however, these translocations have been poorly studied. Here, we present 21 new cases with myelodysplasia, acute myeloid leukemia or CML in blast crisis, which upon karyotyping showed the presence of a t(2;3). Furthermore, an extensive literature review disclosed 29 additional cases. Morphological, clinical and cytogenetic assessment revealed the typical hallmarks of 3q26/EVI1 rearrangements, that is, trilineage dysplasia and dysmegakaryopoiesis, poor prognosis and additional monosomy 7. Molecular cytogenetic analysis and PCR in selected samples indicated that in most cases the translocation indeed targets the EVI1 locus. Mapping of the chromosome 2 breakpoints confirmed the initially suspected cytogenetic breakpoint heterogeneity at the 2p arm.

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References

  1. Morishita K, Parganas E, William CL, Whittaker MH, Drabkin H, Oval J et al. Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300–400 kilobases on chromosome band 3q26. Proc Natl Acad Sci USA 1992; 89: 3937–3941.

    Article  CAS  Google Scholar 

  2. Nucifora G . The EVI1 gene in myeloid leukemia. Leukemia 1997; 11: 2022–2031.

    Article  CAS  Google Scholar 

  3. Peeters P, Wlodarska I, Baens M, Criel A, Selleslag D, Hagemeijer A et al. Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders. Cancer Res 1997; 57: 564–569.

    CAS  Google Scholar 

  4. Barbieri D, Vermaelen K, Van den Berghe H . Preliminary data on the in vitro proliferation pattern and karyotypic characteristics in cells of patients with ANLL. Cancer Genet Cytogenet 1984; 11: 1–9.

    Article  CAS  Google Scholar 

  5. Berger R, Flexor M, Le Coniat M, Derre J, Leblanc T . Translocation (2;3)(p22;q28) is associated with myeloid disorders. Cancer Genet Cytogenet 1995; 79: 130–132.

    Article  CAS  Google Scholar 

  6. Bitter MA, Neilly ME, Le Beau MM, Pearson MG, Rowley JD . Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia. Blood 1985; 66: 1362–1370.

    CAS  PubMed  Google Scholar 

  7. Charrin C, Belhabri A, Treille-Ritouet D, Theuil G, Magaud JP, Fiere D et al. Structural rearrangements of chromosome 3 in 57 patients with acute myeloid leukemia: clinical, hematological and cytogenetic features. Hematol J 2002; 3: 21–31.

    Article  Google Scholar 

  8. Dobrovic A, Morley AA, Seshadri R, Januszewicz EH . Molecular diagnosis of Philadelphia negative CML using the polymerase chain reaction and DNA analysis: clinical features and course of M-bcr negative and M-bcr positive CML. Leukemia 1991; 5: 187–190.

    CAS  PubMed  Google Scholar 

  9. Fleischman EW, Volkova MA, Frenkel MA, Konstantinova LN, Kulagina OE, Baranov AE et al. Translocation (2;3)(p13;q26) in two cases of myeloid malignancies. Acute myeloblastic leukemia (M2) and blastic phase of chronic myeloid leukemia. Cancer Genet Cytogenet 1996; 87: 182–184.

    Article  CAS  Google Scholar 

  10. Herens C, Hermanne JP, Tassin F, Fassotte MF, Thiry A, Jamar M et al. Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary myelofibrosis. Cancer Genet Cytogenet 1999; 110: 62–64.

    Article  CAS  Google Scholar 

  11. Johansson B, Fioretos T, Billstrom R, Mitelman F . Aberrant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-alpha. Leukemia 1996; 10: 1134–1138.

    CAS  PubMed  Google Scholar 

  12. Kwong YL, Chan LC, Lie KW . t(2;3)(p13;q26) in a case of chronic myeloid leukemia. Importance of the involvement of 3q26. Cancer Genet Cytogenet 1992; 59: 95–96.

    Article  CAS  Google Scholar 

  13. Levaltier X, Penther D, Bastard C, Troussard X . t(2;3)(p23;q26) in a patient with AML M2. Br J Haematol 1996; 92: 1027.

    Article  CAS  Google Scholar 

  14. Maciejewski JP, Risitano A, Sloand EM, Nunez O, Young NS . Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. Blood 2002; 99: 3129–3135.

    Article  CAS  Google Scholar 

  15. Mecucci C, Vermaelen K, Tricot G, Louwagie A, Michaux JL, Bosly A et al. 3q−, 3q+ anomaly in malignant proliferations in humans. Cancer Genet Cytogenet 1983; 9: 367–381.

    Article  Google Scholar 

  16. Mrozek K, Heinonen K, Theil KS, Bloomfield CD . Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q. Genes Chromosomes Cancer 2002; 34: 137–153.

    Article  Google Scholar 

  17. Ng A, Taylor GM, Eden OB . Secondary leukemia in a child with neuroblastoma while on oral etoposide: what is the cause? Pediatr Hematol Oncol 2000; 17: 273–279.

    Article  CAS  Google Scholar 

  18. Raynaud SD, Parganas E, Schell U, Grosgeorge J, Nucifora G, Barin C et al. Translocation t(2;3)(p21–22;q26) and myeloid disorders: FISH analysis and molecular study. Blood 1996; 86 (Suppl): 740a.

    Google Scholar 

  19. Rivière D, Pluchon-Rivière E, Talmant P, Pedron M, Lespinasse J, Raynaud S et al. Cytogenetic analysis in patients with primary myelodysplastic syndromes in leukemic transformation. A report of 95 cases. Hematol Cell Ther 1996; 38: 177–181.

    Article  Google Scholar 

  20. Rowley JD, Golomb HM, Vardiman JW . Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. Blood 1981; 58: 759–767.

    CAS  PubMed  Google Scholar 

  21. Van den Berghe H, Vermaelen K, Mecucci C, Barbieri D, Tricot G . The 5q-anomaly. Cancer Genet Cytogenet 1985; 17: 189–255.

    Article  CAS  Google Scholar 

  22. van Lom K, Hagemeijer A, Vandekerckhove F, Smit EM, Lowenberg B . Cytogenetic clonality analysis: typical patterns in myelodysplastic syndrome and acute myeloid leukaemia. Br J Haematol 1996; 93: 594–600.

    Article  CAS  Google Scholar 

  23. Whang-Peng J, Young RC, Lee EC, Longo DL, Schechter GP, DeVita Jr T . Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities. Blood 1988; 71: 403–414.

    CAS  Google Scholar 

  24. Yunis JJ . Recurrent chromosomal defects are found in most patients with acute nonlymphocytic leukemia. Cancer Genet Cytogenet 1984; 11: 125–137.

    Article  CAS  Google Scholar 

  25. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.

    Article  CAS  Google Scholar 

  26. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French–American–British Cooperative Group. Ann Intern Med 1985; 103: 620–625.

    Article  CAS  Google Scholar 

  27. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO). Br J Haematol 1991; 78: 325–329.

    Article  CAS  Google Scholar 

  28. Mitelman F (ed). ISCN (1995). An International System for Human Cytogenetic Nomenclature. Basel: Karger 1995.

  29. Engelen JJ, Die-Smulders CE, Sijstermans JM, Meers LE, Albrechts JC, Hamers AJ . Familial partial trisomy 8p without dysmorphic features and only mild mental retardation. J Med Genet 1995; 32: 792–795.

    Article  CAS  Google Scholar 

  30. Dierlamm J, Wlodarska I, Michaux L, La Starza R, Zeller W, Mecucci C et al. Successful use of the same slide for consecutive fluorescence in situ hybridization experiments. Genes Chromosomes Cancer 1996; 16: 261–264.

    Article  CAS  Google Scholar 

  31. Takahashi E, Koyama K, Hirai M, Itoh H, Nakamura Y . A high-resolution cytogenetic map of human chromosome 2: localization of 434 cosmid markers by direct R-banding fluorescence in situ hybridization. Cytogenet Cell Genet 1995; 68: 112–114.

    Article  CAS  Google Scholar 

  32. Waye JS, Willard HF . Chromosome specificity of satellite DNAs: short- and long-range organization of a diverged dimeric subset of human alpha satellite from chromosome 3. Chromosoma 1989; 97: 475–480.

    Article  CAS  Google Scholar 

  33. Takahashi E, Yamakawa K, Nakamura Y, Hori T . A high-resolution cytogenetic map of human chromosome 3: localization of 291 new cosmid markers by direct R-banding fluorescence in situ hybridization. Genomics 1992; 13: 1047–1055.

    Article  CAS  Google Scholar 

  34. Miki T, Kawamata N, Hirosawa S, Aoki N . Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL6, encodes a Kruppel-like zinc-finger protein. Blood 1994; 83: 26–32.

    CAS  PubMed  Google Scholar 

  35. Poppe B, Dastugue N, De Smet B, Yigit N, De Paepe A, Recher C et al. High resolution molecular cytogenetics and MDS1, MDS1/EVI1 and EVI1 expression patterns in rearrangements involving 3q26. 2004, (in preparation).

  36. Russell M, List A, Greenberg P, Woodward S, Glinsmann B, Parganas E et al. Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations. Blood 1994; 84: 1243–1248.

    CAS  PubMed  Google Scholar 

  37. Mitelman Database of Chromosome Aberrations in Cancer. Mitelman F, Johansson B, Mertens F (eds). http://cgap.nci.nih.gov/Chromosomes/Mitelman, 2003.

  38. Bastard C, Tilly H, Lenormand B, Bigorgne C, Boulet D, Kunlin A et al. Translocations involving band 3q27 and Ig gene regions in non-Hodgkin's lymphoma. Blood 1992; 79: 2527–2531.

    CAS  PubMed  Google Scholar 

  39. Fonatsch C, Gudat H, Lengfelder E, Wandt H, Silling-Engelhardt G, Ludwig WD et al. Correlation of cytogenetic findings with clinical features in 18 patients with inv(3)(q21q26) or t(3;3)(q21;q26). Leukemia 1994; 8: 1318–1326.

    CAS  PubMed  Google Scholar 

  40. Buonamici S, Chakraborty S, Senyuk V, Nucifora G . The role of EVI1 in normal and leukemic cells. Blood Cells Mol Dis 2003; 31: 206–212.

    Article  CAS  Google Scholar 

  41. Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, van Putten WL, Valk PJ, van der Poel-van de Luytgaarde, Hack R et al. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood 2003; 101: 837–845.

    Article  Google Scholar 

  42. Fichelson S, Dreyfus F, Berger R, Melle J, Bastard D, Miclea JM et al. Evi-1 expression in leukemic patients with rearrangements of the 3q25–q28 chromosomal region. Leukemia 1992; 6: 93–99.

    CAS  PubMed  Google Scholar 

  43. Langebeer SE, Rogers JR, Harrison G, Wheatley K, Walker H, Bain BJ et al. EVI1 expression in acute myeloid leukaemia. Br J Haematol 2001; 112: 208–211.

    Article  Google Scholar 

  44. Testoni N, Borsaru G, Martinelli G, Carboni C, Ruggeri D, Ottaviani E et al. 3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features. Haematologica 1999; 84: 690–694.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge Dr GE Beverstock (Leiden University Medical Centre), Dr WPM Breed (Catharina Hospital Eindhoven), Dr SMGJ Daenen (University Hospital Groningen), Dr JC Kluin-Nelemans (Leiden University Medical Center), Dr P Muus (University Medical Center St Radboud Nijmegen), Dr H Schouten (University Hospital Maastricht), Dr GEG Verhoef (University Hospital Leuven), Dr A Van Hoof (AZ St Jan, Brugge), Dr C Dubois (St Jan, Brussels) and Dr P Zachee (Algemeen Centrum Ziekenhuis, Antwerp) for providing all clinical data of their patients, P Meeus and C Brusselmans for review of bone marrow morphology, Josefa Albrechts, Betty Emanuel and Nurten Yigit for technical support and R Logist for help in preparing the paper. This text presents research results of the Belgian program of Interuniversity Poles of attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The scientific responsibility is assumed by the authors. This study was partially supported by the Fund for Scientific Research of Flanders (FWO – Vlaanderen), Grant No. G.0310.01. Bruce Poppe is a research fellow of the Fund for Scientific Research of Flanders.

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  1. M Stevens-Kroef and B Poppe: These two authors share first authorship

Authors and Affiliations

  1. Department of Clinical Genetics, University Hospital Maastricht, The Netherlands

    M Stevens-Kroef, M van der Blij-Philipsen & G Hamers

  2. Department of Medical Genetics, Ghent University, Ghent, Belgium

    B Poppe & F Speleman

  3. Department of Clinical Cytogenetics, Leiden University Medical Center, The Netherlands

    S van Zelderen-Bhola

  4. Department of Medical Genetics, University of Groningen, The Netherlands

    E van den Berg

  5. Department of Human Genetics, University Medical Center Nijmegen, The Netherlands

    A Geurts van Kessel

  6. Departments of Clinical Genetics and of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands

    R Slater

  7. Center for Human Genetics, University of Leuven, Belgium

    L Michaux & A Hagemeijer

  8. Department of Hematology, Cliniques Universitaires UCL St Luc, Brussels, Belgium

    L Michaux

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Correspondence to A Hagemeijer.

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Stevens-Kroef, M., Poppe, B., van Zelderen-Bhola, S. et al. Translocation t(2;3)(p15–23;q26–27) in myeloid malignancies: report of 21 new cases, clinical, cytogenetic and molecular genetic features. Leukemia 18, 1108–1114 (2004). https://doi.org/10.1038/sj.leu.2403346

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