Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Post-Transplant Events

Cytogenetic evolution patterns in CML post-SCT

Abstract

The cytogenetic evolution patterns in chronic myeloid leukemia (CML) after allogeneic (allo) stem cell transplantation (SCT) are different from the ones observed in non-transplanted patients, a phenomenon suggested to be caused by the conditioning regime. We reviewed 131 CMLs displaying karyotypic evolution after SCT (122 allo, nine autologous (auto)), treated at Lund University Hospital or reported in the literature. Major route abnormalities (i.e., +8, +Ph, i(17q), +19, +21, +17 and −7) were seen in 14%, balanced aberrations in 61%, hyperdiploidy in 19%, pseudodiploidy in 79%, divergent clones in 14%, and Ph-negative clones in 21%. The breakpoints involved in secondary structural rearrangements clustered at 1q21, 1q32, 7q22, 9q34, 11q13, 11q23, 12q24, 13q14, 17q10 and 22q11. Cytogenetic abnormalities common in AML after genotoxic exposure, that is, der(1;7)(q10;p10), del(3p), −5, del(5q), −7, −17, der(17p), −18, and −21, were only rarely seen post-SCT. Comparing the cytogenetic features in relation to type of SCT revealed that balanced aberrations were significantly more common after allo than after auto SCT (64 and 22%, respectively, P=0.03). In addition, there was a trend as regards hyperdiploidy being more common after auto (P=0.07) and pseudodiploidy being more frequent after allo SCT (P=0.09). Possible reasons for these differences are discussed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Deininger MW, Goldman JM, Melo JV . The molecular biology of chronic myeloid leukemia. Blood 2000; 96: 3343–3356.

    CAS  PubMed  Google Scholar 

  2. Johansson B, Fioretos T, Mitelman F . Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 2002; 107: 76–94.

    Article  CAS  Google Scholar 

  3. Swolin B, Weinfeld A, Westin J, Waldenström J, Magnusson B . Karyotypic evolution in Ph-positive chronic myeloid leukemia in relation to management and disease progression. Cancer Genet Cytogenet 1985; 18: 65–79.

    Article  CAS  Google Scholar 

  4. Johansson B, Fioretos T, Billström R, Mitelman F . Abberant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-α. Leukemia 1996; 10: 1134–1138.

    CAS  PubMed  Google Scholar 

  5. Maloisel F, Uettwiller F, Laplace A, Lioure B, Herbrecht R, Mark M et al. Emergence of unusual cytogenetic abnormalities under interferon-alpha therapy in patients with chronic myelogenous leukemia. Cancer Genet Cytogenet 1999; 113: 172–176.

    Article  CAS  Google Scholar 

  6. Casali M, Truglio F, Milone G, Di Raimondo F, Parrinello G, Maserati E et al. Trisomy 8 in Philadelphia chromosome (Ph1)-negative cells in the course of Ph1-positive chronic myelocytic leukemia. Genes Chromosomes Cancer 1992; 4: 269–270.

    Article  CAS  Google Scholar 

  7. Bilhou-Nabera C, Marit G, Devianne I, Viard F, Salzes S, Montastruc M et al. A second case of trisomy 8 in Philadelphia chromosome (Ph)-negative cells during the course of Ph-positive chronic myelocytic leukemia. Genes Chromosomes Cancer 1993; 6: 255–256.

    Article  CAS  Google Scholar 

  8. Ariyama T, Inazawa J, Uemura Y, Kakazu N, Maekawa T, Urase F et al. Clonal origin of Philadelphia chromosome negative cells with trisomy 8 appearing during the course of α-interferon therapy for Ph positive chronic myelocytic leukemia. Cancer Genet Cytogenet 1995; 81: 20–23.

    Article  CAS  Google Scholar 

  9. Fayad L, Kantarjian H, O'Brien S, Seong D, Albitar M, Keating M et al. Emergence of new clonal abnormalities following interferon-alpha induced complete cytogenetic response in patients with chronic myeloid leukemia: report of three cases. Leukemia 1997; 11: 767–771.

    Article  CAS  Google Scholar 

  10. Andersen MK, Pedersen-Bjergaard J, Kjeldsen L, Dufva IH, Brøndum-Nielsen K . Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8. Leukemia 2002; 16: 1390–1393.

    Article  CAS  Google Scholar 

  11. Braziel RM, Launder TM, Druker BJ, Olson SB, Magenis RE, Mauro MJ et al. Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients: 14 months' experience. Blood 2002; 100: 435–441.

    Article  CAS  Google Scholar 

  12. Meeus P, Demuynck H, Martiat P, Michaux L, Wouters E, Hagemeijer A . Sustained, clonal karyotype abnormalities in the Philadelphia chromosome negative cells of CML patients successfully treated with Imatinib. Leukemia 2003; 17: 465–467.

    Article  CAS  Google Scholar 

  13. O'Dwyer ME, Gatter KM, Loriaux M, Druker BJ, Olson SB, Magenis RE et al. Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate. Leukemia 2003; 17: 481–487.

    Article  CAS  Google Scholar 

  14. Feldman E, Najfeld V, Schuster M, Roboz G, Chadburn A, Silver RT . The emergence of Ph, trisomy -8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate. Exp Hematol 2003; 31: 702–707.

    Article  CAS  Google Scholar 

  15. Medina J, Kantarjian H, Talpaz M, O'Brien S, Garcia-Manero G, Giles F et al. Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Cancer 2003; 98: 1905–1911.

    Article  CAS  Google Scholar 

  16. Bumm T, Müller C, Al-Ali HK, Krohn K, Shepherd P, Schmidt E et al. Emergence of clonal cytogenetic abnormalities in Ph cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority. Blood 2003; 101: 1941–1949.

    Article  CAS  Google Scholar 

  17. Terre C, Eclache V, Rousselot P, Imbert M, Charrin C, Gervais C et al. Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia. Leukemia 2004; 18: 1340–1346.

    Article  CAS  Google Scholar 

  18. da Silva MA, Heerema NA, Lowe LR, Tricot G, Jansen J . Cytogenetic patterns following bone marrow transplantation for chronic granulocytic leukemia. Cancer Genet Cytogenet 1988; 36: 35–44.

    Article  CAS  Google Scholar 

  19. Calabrese G, Di Bartolomeo P, Stuppia L, Guanciali Franchi P, Parruti G, Ciancarelli M et al. Cytogenetics in patients with chronic myelogenous leukemia treated with bone marrow transplantation. Cancer Genet Cytogenet 1989; 41: 49–59.

    Article  CAS  Google Scholar 

  20. Sessarego M, Frassoni F, Defferrari R, Bacigalupo A, Miceli S, Mareni C et al. Cytogenetic follow-up after bone marrow transplantation for Philadelphia-positive chronic myeloid leukemia. Cancer Genet Cytogenet 1989; 42: 253–261.

    Article  CAS  Google Scholar 

  21. Alimena G, De Cuia MR, Mecucci C, Arcese W, Mauro F, Screnci M et al. Cytogenetic follow-up after allogeneic bone-marrow transplantation for Ph1-positive chronic myelogenous leukemia. Bone Marrow Transplant 1990; 5: 119–127.

    CAS  PubMed  Google Scholar 

  22. Offit K, Burns JP, Cunningham I, Jhanwar SC, Black P, Kernan NA et al. Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation. Blood 1990; 75: 1346–1355.

    CAS  PubMed  Google Scholar 

  23. Shah NK, Wagner J, Santos G, Griffin CA . Karyotype at relapse following allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cancer Genet Cytogenet 1992; 61: 183–192.

    Article  CAS  Google Scholar 

  24. Sessarego M, Frassoni F, Defferrari R, Bacigalupo A, Fugazza G, Mareni C et al. Karyotype evolution of Ph positive chronic myelogenous leukemia patients relapsed in advanced phases of the disease after allogeneic bone marrow transplantation. Cancer Genet Cytogenet 1991; 57: 69–78.

    Article  CAS  Google Scholar 

  25. Bilhou-Nabera C, Bernard P, Marit G, Viard F, Gharbi MJ, Wen Z et al. Serial cytogenetic studies in allografted patients with chronic myeloid leukemia. Bone Marrow Transplant 1992; 9: 263–268.

    CAS  PubMed  Google Scholar 

  26. Chase A, Pickard J, Szydlo R, Coulthard S, Goldman JM, Cross NCP . Non-random involvement of chromosome 13 in patients with persistent or relapsed disease after bone-marrow transplantation for chronic myeloid leukemia. Genes Chromosomes Cancer 2000; 27: 278–284.

    Article  CAS  Google Scholar 

  27. Mitelman F, Johansson B, Mertens F . Mitelman database of chromosome aberrations in cancer. (updated 10 July 2006). Available from: http://cgap.nci.nih.gov/Chromosomes/Mitelman.

  28. Shaffer LG, Tommerup N (eds). ISCN 2005. An International System for Human Cytogenetic Nomenclature. S. Karger: Basel, 2005.

  29. Palka G, Di Bartolomeo P, Iacone A, Di Girolamo G, Betti S, Calabrese G . et al. Cytogenetics and bone marrow transplantation. Cancer Genet Cytogenet 1986; 21: 147–157.

    Article  CAS  Google Scholar 

  30. Huret JL, Schoenwald M, Brizard A, Guilhot F, Vilmer E, Tanzer J . Chromosome 6p rearrangements appear to be secondary changes in various haematological malignancies. Leuk Res 1989; 13: 819–824.

    Article  CAS  Google Scholar 

  31. Secker-Walker LM, Cooke HM, Browett PJ, Norton JD, Kitchen C, Prentice AG et al. Clonal evolution in Ph-negative, bcr-positive chronic myeloid leukaemia before and after bone marrow transplantation. Acta Haematol 1989; 82: 205–209.

    Article  CAS  Google Scholar 

  32. Melnyk A, Kowal-Vern A . Complex translocations in a patient with chronic myelocytic leukemia: t(9;22;17) and t(10;18;19) after two failed bone marrow transplantations. Cancer Genet Cytogenet 1990; 46: 83–87.

    Article  CAS  Google Scholar 

  33. Gilliland G, Patterson EJ, Rosenthal DS, Tantravahi R . Multiple clones with (3;21) translocation in a case of Ph-positive chronic myelogenous leukemia during relapse after allogeneic bone marrow transplantation. Cancer Genet Cytogenet 1990; 47: 55–60.

    Article  CAS  Google Scholar 

  34. Hild F, Fonatsch C . Cytogenetic peculiarities in chronic myelogenous leukemia. Cancer Genet Cytogenet 1990; 47: 197–217.

    Article  CAS  Google Scholar 

  35. Lawler SD, Khokhar MT, Davies H, Williams GJ, Powles R . Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts. Cancer Genet Cytogenet 1990; 47: 249–263.

    Article  CAS  Google Scholar 

  36. Kerim S, Stul M, Mecucci C, Vandenberghe E, Cuneo A, Cin PD et al. Rearrangement of immunoglobulin and TCR genes in lymphoid blast crisis of Ph+ chronic myeloid leukaemia. Br J Haematol 1990; 74: 414–419.

    Article  CAS  Google Scholar 

  37. Agaliotis DP, Papenhausen PR, Moscinski LC, Elfenbein GJ . Case report of spontaneous remission of cytogenetic relapse of chronic myelogenous leukemia suggestive of progression to blast crisis after allogeneic bone marrow transplantation. Ann Hematol 1995; 70: 37–41.

    Article  CAS  Google Scholar 

  38. Soligo D, Romitti L, Bertolli V, Della Volpe A, Annaloro C, Lambertenghi Deliliers G . 5q- in a case of chronic myelogenous leukemia relapsed after allogeneic bone marrow transplantation. Haematologica 1995; 80: 437–439.

    CAS  PubMed  Google Scholar 

  39. Yehuda O, Abeliovich D, Ben-Neriah S, Sverdlin I, Cohen R, Varadi G et al. Clinical implications of fluorescence in situ hybridization analysis in 13 chronic myeloid leukemia cases: Ph-negative and variant Ph-positive. Cancer Genet Cytogenet 1999; 114: 100–107.

    Article  CAS  Google Scholar 

  40. Zhou M, Sheldon S, Akel N, Killeen AA . Chromosomal aneuploidy in leukemic blast crisis: a potential source of error in interpretation of bone marrow engraftment analysis by VNTR amplification. Mol Diagn 1999; 4: 153–157.

    Article  CAS  Google Scholar 

  41. Ahuja HG, Popplewell L, Tcheurekdjian L, Slovak ML . NUP98 gene rearrangements and the clonal evolution of chronic myelogenous leukemia. Genes Chromosomes Cancer 2001; 30: 410–415.

    Article  CAS  Google Scholar 

  42. Zaccaria A, Rosti G, Testoni N, Alimena G, Arcese W, Bandini G et al. Chromosome studies in patients with Philadelphia chromosome-positive chronic myeloid leukemia submitted to bone marrow transplantation--results of a European Cooperative Study. Cancer Genet Cytogenet 1987; 26: 5–13.

    Article  CAS  Google Scholar 

  43. Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S et al. Identification of four new translocations involving FGFR1 in myeloid disorders. Genes Chromosomes Cancer 2001; 32: 155–163.

    Article  CAS  Google Scholar 

  44. Fefer A, Cheever MA, Thomas ED, Boyd C, Ramberg R, Glucksberg H et al. Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin. N Engl J Med 1979; 300: 333–337.

    Article  CAS  Google Scholar 

  45. Goldman JM, Apperley JF, Jones L, Marcus R, Goolden AW, Batchelor R et al. Bone marrow transplantation for patients with chronic myeloid leukemia. N Engl J Med 1986; 314: 202–207.

    Article  CAS  Google Scholar 

  46. Zaccaria A, Rosti G, Sessarego M, Frassoni F, Marmont A, Galimberti M et al. Relapse after allogeneic bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia: cytogenetic analysis of 24 patients. Bone Marrow Transplant 1988; 3: 413–423.

    CAS  PubMed  Google Scholar 

  47. Cooperative Study Group on Chromosomes in Transplanted Patients. Cytogenetic follow-up of 100 patients submitted to bone marrow transplantation for Philadelphia chromosome-positive chronic myeloid leukemia. Eur J Haematol 1988; 40: 50–57.

    Google Scholar 

  48. Okazuka K, Toba K, Kawai K, Nikkuni K, Tsuchiyama J, Momoi A et al. Extramedullary T lymphoid blast crisis representing an additional translocation, t(6;8)(q25;q22) in a patient with Philadelphia-positive chronic myelogenous leukemia after allogeneic bone marrow transplantation. Leuk Res 2001; 25: 1089–1094.

    Article  CAS  Google Scholar 

  49. Consoli U, Milone G, Guido G, Consoli C, Palumbo GA, Giustolisi R . STI571 (Glivec) induced hematologic, cytogenetic and molecular remission in a chronic myeloid leukemia patient relapsing with accelerated phase after allogeneic stem cell transplantation. Haematologica 2002; 87: ECR37.

    PubMed  Google Scholar 

  50. Herens C, Baron F, Croisiau C, Tassin F, Bours V . Clonal chromosome aberrations in Philadelphia-negative cells from chronic myelocytic leukemia patients treated with imatinib mesylate: report of two cases. Cancer Genet Cytogenet 2003; 147: 78–80.

    Article  CAS  Google Scholar 

  51. Gozzetti A, Tozzuoli D, Crupi R, Gentili S, Bocchia M, Raspadori D et al. Emergence of Ph negative clones in chronic myeloid leukemia (CML) patients in complete cytogenetic remission after therapy with imatinib mesylate (STI). Eur J Haematol 2003; 71: 313–314.

    Article  Google Scholar 

  52. Jacob A, Griffiths M, Larkins S, Holmes J . t(3;21) following peripheral blood stem cell transplantation in chronic phase chronic myeloid leukaemia. Bone Marrow Transplant 1997; 19: 1255–1258.

    Article  CAS  Google Scholar 

  53. Morel F, Bris MJ, Herry A, Calvez GL, Marion V, Abgrall JF et al. Double minutes containing amplified bcr-abl fusion gene in a case of chronic myeloid leukemia treated by imatinib. Eur J Haematol 2003; 70: 235–239.

    Article  Google Scholar 

  54. Athanasiadou A, Stavroyianni N, Saloum R, Asteriou O, Anagnostopoulos A, Fassas A . Novel chromosomal aberrations in Philadelphia negative cells of chronic myelogenous leukemia patients on imatinib: report of three cases. Leukemia 2004; 18: 1029–1031.

    Article  CAS  Google Scholar 

  55. Mauritzson N, Albin M, Rylander L, Billström R, Ahlgren T, Mikoczy Z 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.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was funded by grants from the Swedish Cancer Society, the Swedish Children's Cancer Foundation, and the Swedish Research Council.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K Karrman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karrman, K., Sallerfors, B., Lenhoff, S. et al. Cytogenetic evolution patterns in CML post-SCT. Bone Marrow Transplant 39, 165–171 (2007). https://doi.org/10.1038/sj.bmt.1705560

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705560

Keywords

This article is cited by

Search

Quick links