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Acute Myeloid Leukemia Following a Myeloproliferative Neoplasm: Clinical Characteristics, Genetic Features and Effects of Therapy

  • Acute Leukemias (E Feldman, Section Editor)
  • Published:
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Abstract

Acute myeloid leukemia (AML) is an uncommon, but often deadly complication of myeloproliferative neoplasms (MPN). Post-MPN AML usually occurs years after the initial MPN diagnosis with an average age of onset between 64 and 68 years. Chromosome abnormalities are common and many patients have cytogenetic changes that are associated with poor risk features. Post-MPN AML is characterized by acquired somatic gene mutations, but, interestingly, mutations thought to have an etiologic role in the MPN, such as JAK2V617F, are sometimes absent in the AML clone. Conventional AML-style treatment appears to have limited efficacy, although when coupled to allogeneic stem cell transplantation, some patients have long-term survival. Less-intensive therapies such as hypomethylating agents and the JAK inhibitor, ruxolitinib, may be effective in some patients. New treatments have prompted efforts to characterize therapeutic responses better.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054–61.

    PubMed  CAS  Google Scholar 

  2. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387–97.

    Article  PubMed  CAS  Google Scholar 

  3. Zhao R, Xing S, Li Z, et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem. 2005;280:22788–92.

    Article  PubMed  CAS  Google Scholar 

  4. Druker BJ. Perspectives on the development of imatinib and the future of cancer research. Nat Med. 2009;15:1149–52.

    Article  PubMed  CAS  Google Scholar 

  5. Skversky NJ, Yarrow MW, Lewinn EB. Phenylbutazone in the treatment of deep-vein thrombophlebitis; a preliminary report. J Albert Einstein Med Cent (Phila). 1957;5:268–71.

    CAS  Google Scholar 

  6. Bank A, Larsen PR, Anderson HM. Di Guglielmo’s syndrome after polycythemia. N Engl J Med. 1966;275:489–90.

    Article  PubMed  CAS  Google Scholar 

  7. Passamonti F, Rumi E, Arcaini L, et al. Leukemic transformation of polycythemia vera: a single center study of 23 patients. Cancer. 2005;104:1032–6.

    Article  PubMed  Google Scholar 

  8. Mesa RA, Li CY, Ketterling RP, et al. Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood. 2005;105:973–7.

    Article  PubMed  CAS  Google Scholar 

  9. Tam CS, Nussenzveig RM, Popat U, et al. The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms. Blood. 2008;112:1628–37.

    Article  PubMed  CAS  Google Scholar 

  10. Abdulkarim K, Girodon F, Johansson P, et al. AML transformation in 56 patients with Ph-MPD in two well defined populations. Eur J Haematol. 2009;82:106–11.

    Article  PubMed  Google Scholar 

  11. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22:14–22.

    Article  PubMed  CAS  Google Scholar 

  12. Campbell PJ, Baxter EJ, Beer PA, et al. Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood. 2006;108(10):3548–55.

    Article  PubMed  CAS  Google Scholar 

  13. •• Beer PA, Delhommeau F, LeCouedic JP, et al. Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood. 2010;115:2891–900. This study investigated the evolution of the acute leukemic clone from a cell that was evolutionarily distinct from the MPN clone.

  14. •• Abdel-Wahab O, Manshouri T, Patel J, et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res. 2010;70:447–52. Genetic analysis of 63 patients with post-MPN AML identifying TET2, AXL1 and IDH1 in addition to JAK2 as common mutations.

    Article  PubMed  CAS  Google Scholar 

  15. Harutyunyan A, Klampfl T, Cazzola M, Kralovics R. p53 lesions in leukemic transformation. New Engl J Med. 2011;364:488–90.

    Article  PubMed  CAS  Google Scholar 

  16. Ding Y, Harada Y, Imagawa J, Kimura A, Harada H. AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood. 2009;114(25):5201–5.

    Article  PubMed  CAS  Google Scholar 

  17. Puda A, Milosevic JD, Berg T, et al. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. Am J Hematol. 2012;87:245–50.

    Article  PubMed  CAS  Google Scholar 

  18. Zhang SJ, Rampal R, Manshouri T, et al. Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome. Blood. 2012;119:4480–5.

    Article  PubMed  CAS  Google Scholar 

  19. Abdel-Wahab O, Pardanani A, Rampal R, et al. DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia. 2011;25:1219–20.

    Article  PubMed  CAS  Google Scholar 

  20. Tefferi A, Lasho TL, Abdel-Wahab O, et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia. 2010;24:1302–9.

    Article  PubMed  CAS  Google Scholar 

  21. •• Thoennissen NH, Krug UO, Lee DH, Kawamata N, Iwanski GB, Lasho T, et al. Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms. Blood. 2010;115:2882–90. Analysis of 71 patients with post-MPN-AML identified established targets such as ETV6, p53 and RUNX1 and also identified new candidate genes.

    Article  PubMed  CAS  Google Scholar 

  22. Berk PD, Goldberg JD, Silverstein MN, et al. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med. 1981;304:441–7.

    Article  PubMed  CAS  Google Scholar 

  23. Fruchtman SM, Mack K, Kaplan ME, et al. From efficacy to safety: a Polycythemia Vera Study group report on hydroxyurea in patients with polycythemia vera. Semin Hematol. 1997;34:17–23.

    PubMed  CAS  Google Scholar 

  24. Finazzi G, Caruso V, Marchioli R, et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005;105:2664–70.

    Article  PubMed  CAS  Google Scholar 

  25. Bjorkholm M, Derolf AR, Hultcrantz M, et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J Clin Oncol. 2011;29:2410–5.

    Article  PubMed  Google Scholar 

  26. Huang J, Li CY, Mesa RA, et al. Risk factors for leukemic transformation in patients with primary myelofibrosis. Cancer. 2008;112:2726–32.

    Article  PubMed  Google Scholar 

  27. Cherington C, Slack JL, Leis J, et al. Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase. Leuk Res. 2012;36:1147–51.

    Article  PubMed  Google Scholar 

  28. Mascarenhas J, Roper N, Chaurasia P, Hoffman R. Epigenetic abnormalities in myeloproliferative neoplasms: a target for novel therapeutic strategies. Clin Epigenetics. 2011;2:197–212.

    Article  PubMed  CAS  Google Scholar 

  29. •• Thepot S, Itzykson R, Seegers V, et al. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010;116:3735–42. Treatment of patients with post-MPN AML with the hypomethylating agent, azacytidine, resulted in a complete response in 24 % and an overall response rate of 52 %.

    Article  PubMed  CAS  Google Scholar 

  30. Mascarenhas J, Navada S, Malone A, et al. Therapeutic options for patients with myelofibrosis in blast phase. Leuk Res. 2010;34:1246–9.

    Article  PubMed  Google Scholar 

  31. •• Eghtedar A, Verstovsek S, Estrov Z, et al. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012;119:4614–8. In this phase 2 study, 3 of 16 patients achieved either a complete response or a complete response with incomplete blood count recovery with the JAK inhibitor, ruxolitinib, and a total of 60 % appeared to have clinical benefit.

    Article  PubMed  CAS  Google Scholar 

  32. •• Mascarenhas J, Heaney ML, Najfeld V, et al. Proposed criteria for response assessment in patients treated in clinical trials for myeloproliferative neoplasms in blast phase (MPN-BP): formal recommendations from the post-myeloproliferative neoplasm acute myeloid leukemia consortium. Leuk Res. 2012;36:1500–4. Proposal for a new response classification specific for post-MPN AML that encompasses responses of both the blastic component and the underlying MPN.

    Article  PubMed  Google Scholar 

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Disclosure

M. Heaney: consultant for Incyte, Novartis, received payment for development of educational presentations from Medicom Worldwide, and received reimbursement of travel/accommodation expenses from Incyte, Novartis. G. Soriano: none.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Columbia University Medical Center, Herbert Irving Pavilion 9-098 161 Fort Washington Ave, New York, NY, 10032, USA

    Mark L. Heaney

  2. Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY, 10065, USA

    Gabriela Soriano

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  1. Mark L. Heaney
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  2. Gabriela Soriano
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Correspondence to Mark L. Heaney.

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Heaney, M.L., Soriano, G. Acute Myeloid Leukemia Following a Myeloproliferative Neoplasm: Clinical Characteristics, Genetic Features and Effects of Therapy. Curr Hematol Malig Rep 8, 116–122 (2013). https://doi.org/10.1007/s11899-013-0154-5

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  • DOI: https://doi.org/10.1007/s11899-013-0154-5

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