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Cytogenetic response to imatinib treatment in Southern Brazilian patients with chronic myelogenous leukemia and variant Philadelphia chromosome

Annals of Hematology volume 92, pages 185–189 (2013)Cite this article

Abstract

Variant Philadelphia (Ph) chromosome can be observed in 5–10 % of chronic myelogenous leukemia (CML) patients. However, there are only a few studies which have analyzed the prognostic implications of these complex translocations in CML patients after the advent of imatinib mesylate and the results found are conflicting. We investigated the clinical features and cytogenetic response of Brazilian chronic phase (CP) CML patients with variant Ph treated with imatinib mesylate. Among 93 CP CML patients, eight (8.6 %) exhibited complex translocations, involving one (n = 6), two (n = 1), or three (n = 1) additional chromosomes. At 6, 12, and 18 months, a complete cytogenetic response was observed in 100 % of variant Ph patients, respectively. No significant difference was found between variant Ph and standard translocation patients regarding the response to IM treatment at 6, 12, and 18 months. Likewise, there was no statistically significant difference between the two groups concerning the overall survival, failure-free survival, progression-free survival, and event-free survival. The results obtained in our study, despite our sample size, suggest, in agreement to other data found in the literature, that the presence of variant Philadelphia chromosome does not bestow a prognostic disadvantage when compared to the group with classic Ph. This observation does not suggest the need to adjust the treatment protocol due to the presence of variant Ph. However, further studies with larger sample sizes and evaluating both the cytogenetic and molecular response to IM treatment should be conducted to confirm our findings.

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References

  1. Abramson S, Miller RG, Phillips RA (1971) The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J Exp Med 145(6):1567–1579

    Article  Google Scholar 

  2. Deininger MW, Goldman JM, Melo JV (2000) The molecular biology of chronic myeloid leukemia. Blood 96(10):3343–3356

    PubMed  CAS  Google Scholar 

  3. Sessions J (2007) Chronic myeloid leukemia in 2007. J Manag Care Pharm 13(8 Suppl A):4–7

    PubMed  Google Scholar 

  4. Rowley JD (1973) A new consistent abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243(5405):290–293

    PubMed  Article  CAS  Google Scholar 

  5. Rubnitz JE, Gibson B, Smith FO (2008) Acute myeloid leukemia. Pediatr Clin N Am 55(1):21–51

    Article  Google Scholar 

  6. Heim S, Mitelman F (2009) Cancer cytogenetics, 3rd edn. Willey, New York

    Google Scholar 

  7. Pavlovsky C, Kantarjian H, Cortes JE (2009) First-line therapy for chronic myeloid leukemia: past, present, and future. Am J Hematol 84(5):287–293

    PubMed  Article  CAS  Google Scholar 

  8. Bartram CR, de Klein A, Hagemeijer A, van Agthoven T, Geurts van Kessel A, Bootsma D et al (1983) Translocation of c-abl oncogene correlates with the presence of a Philadelphia chromossome in cronic myelocitic leukemia. Nature 306:277–280

    Google Scholar 

  9. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G (1984) Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36(1):93–99

    PubMed  Article  CAS  Google Scholar 

  10. Konopka JB, Watanabe SM, Witte ON (1984) An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell 37(3):1035–1042

    PubMed  Article  CAS  Google Scholar 

  11. Heisterkamp N, Stam K, Groffen J, de Klein A, Grosveld G (1985) Structural organization of the bcr gene and its role in the Ph’ translocation. Nature 315(6022):758–761

    PubMed  Article  CAS  Google Scholar 

  12. Shtivelman E, Lifshitz B, Gale RP, Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 315(6020):550–554

    PubMed  Article  CAS  Google Scholar 

  13. Lugo TG, Pendergast AM, Muller AJ, Witte ON (1990) Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247(4946):1079–1082

    PubMed  Article  CAS  Google Scholar 

  14. Sattler M, Griffins JD (2003) Molecular mechanisms of transformation by the bcr-abl oncogene. Semin Hematol 40(2 Suppl 2):4–10

    PubMed  Article  CAS  Google Scholar 

  15. Bernstein R, Pinto MR, Wallace C, Penfold G, Mendelow B (1984) The incidence, type, and subsequent evolution of 14 variant Ph1 translocations in 180 South African patients with Ph1-positive chronic myeloid leukemia. Cancer Genet Cytogenet 12(3):225–238

    PubMed  Article  CAS  Google Scholar 

  16. Kadam PR, Nanjangud GJ, Advani SH (1990) The occurrence of variant Ph translocations in chronic myeloid leukemia (CML): a report of six cases. Hematol Oncol 8(6):303–312

    PubMed  Article  CAS  Google Scholar 

  17. Quintás-Cardama A, Cortes JE (2006) Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc 81:973–988

    PubMed  Article  Google Scholar 

  18. Hochhaus A (2011) Educational session: managing chronic myeloid leukemia as a chronic disease. Hematol Am Soc Hematol Educ Program 2011:128–135

    Article  Google Scholar 

  19. Shaffer LG, Slovak ML, Campbell LJ (2009) ISCN 2009: an International System for Human Cytogenetic Nomenclature (2009): Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Karger, Basel

    Google Scholar 

  20. Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J et al (2009) Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 27(35):6041–6051

    PubMed  Article  CAS  Google Scholar 

  21. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE et al (1984) Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 63(4):789–799

    PubMed  CAS  Google Scholar 

  22. El-Zimaity MM, Kantarjian H, Talpaz M, O’Brien S, Giles F, Garcia-Manero G et al (2004) Results of imatinib mesylate therapy in chronic myelogenous leukaemia with variant Philadelphia chromosome. Br J Haematol 125(2):187–195

    PubMed  Article  CAS  Google Scholar 

  23. Marzocchi G, Castagnetti F, Luatti S, Baldazzi C, Stacchini M, Gugliotta G et al (2011) Variant Philadelphia translocations: molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA Working Party on CML analysis. Blood 117(25):6793–6800

    PubMed  Article  CAS  Google Scholar 

  24. Fabarius A, Leitner A, Hochhaus A, Muller MC, Hanfstein B, Haferlach C et al (2011) Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood 118:6760–6768

    PubMed  Article  CAS  Google Scholar 

  25. Stagno F, Vigneri P, Del Fabro V, Stella S, Cupri A, Massimino M et al (2010) Influence of complex variant chromosomal translocations in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Acta Oncol 49(4):506–508

    PubMed  Article  CAS  Google Scholar 

  26. Berger U, Maywald O, Pfirrmann M, Lahaye T, Hochhaus A, Reiter A et al (2005) Gender aspects in chronic myeloid leukemia: long-term results from randomized studies. Leukemia 19:984–989

    PubMed  Article  CAS  Google Scholar 

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Affiliations

  1. Clinical Genetics and Graduate Program of Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite 245/403, Porto Alegre, 90050-170, RS, Brazil

    Dayane B. Koshiyama, Giorgio A. Paskulin, Rafael F. M. Rosa & Paulo R. G. Zen

  2. Hematology–Oncology Division, Grupo Hospitalar Conceição, Porto Alegre, RS, Brazil

    Marcelo E. Z. Capra & Tito Vanelli

  3. Institute of Education and Research, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil

    Ceres A. V. Oliveira

  4. Hematology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Laura M. Fogliatto

Authors
  1. Dayane B. Koshiyama
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  2. Marcelo E. Z. Capra
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  3. Giorgio A. Paskulin
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  4. Rafael F. M. Rosa
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  5. Ceres A. V. Oliveira
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  6. Tito Vanelli
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  7. Laura M. Fogliatto
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  8. Paulo R. G. Zen
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Correspondence to Paulo R. G. Zen.

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Koshiyama, D.B., Capra, M.E.Z., Paskulin, G.A. et al. Cytogenetic response to imatinib treatment in Southern Brazilian patients with chronic myelogenous leukemia and variant Philadelphia chromosome. Ann Hematol 92, 185–189 (2013). https://doi.org/10.1007/s00277-012-1598-8

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  • DOI: https://doi.org/10.1007/s00277-012-1598-8

Keywords

  • Variant Ph
  • CML
  • Complex translocation
  • Imatinib mesylate