Blastic Transformation of BCR-ABL-Negative Myeloproliferative Neoplasms

  • Madappa N. Kundranda
  • Raoul Tibes
  • Ruben A. Mesa
Part of the Hematologic Malignancies book series (HEMATOLOGIC)


The BCR-ABL-negative myeloproliferative neoplasms (MPNs) of essential thrombocythemia, polycythemia vera, and primary myelofibrosis have an increasing predisposition over the course of a patient’s illness to transform to overt acute leukemia what is referred to as MPN-Blast Phase (MPN-BP). Although the transformation of MPNs into acute leukemia is by itself a very rare phenomenon, once this has occurred, it is associated with poor response to chemotherapy and a high risk of relapse after allogeneic stem cell transplant (ASCT) and hence resulting in very poor survival in most cases. Pathogenetic mechanisms which lead to an MPN progressing to MPN-BP are incompletely understood but seem to correlate with accumulation of additional karyotypic abnormalities as opposed to increases in MPN-associated molecular lesion burden (such as JAK2 V617F). The development of MPN-BP is heralded by worsening cytopenias, constitutional symptoms, and a very poor survival despite therapeutic intervention. Risk factors for developing MPN-BP include both features at diagnosis (such as increased peripheral blood blasts, karyotypic abnormalities, and thrombocytopenia), as well as exposure to established agents which enhance leukemogenesis (i.e., P-32 and alkylators). Current therapies for the MPNs are limited, and no therapy other than an ASCT has clearly altered the natural history of these neoplasms. Therefore, an overall management plan that incorporates the possibility of ASCT should be developed for patients with MPN-BP at the time of diagnosis. However, it is not all dark and gray in the MPN-BP world; in last 6 years, we have made more advances in the treatment of MPNs than in the last 60 years. Multiple avenues of therapeutic investigation are ongoing to treat, or prevent, MPN-BP including early allogeneic stem cell transplantation, hypomethylating agents, and JAK2 inhibition.


Acute Myeloid Leukemia JAK2 V617F JAK2 V617F Mutation Blast Phase Leukemic Transformation 
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.



Atypical chronic myeloid leukemia


Acute myeloid leukemia


Allogeneic stem cell transplant


Additional sex combs-like 1


Adenosine triphosphate


Chronic myelomonocytic leukemia


Complete response


Erythroid stimulating agent


Essential thrombocythemia


Histone deacetylase


Hedgehog pathway inhibitors


Hematopoietic stem cell transplant


Interferon consensus sequence binding protein


Isocitrate dehydrogenase


IKAROS family zinc finger 1


International Prognostic Scoring System


International Working Group for Myelofibrosis Research and Treatment


Myeloproliferative leukemia


Myeloproliferative neoplasm


Myeloproliferative neoplasm blast phase


Mammalian target of rapamycin


Nonhomologous end joining


Philadelphia (chromosome)


Primary myelofibrosis


Polycythemia vera


Reactive oxygen species


Single nucleotide polymorphism analysis


World Health Organization


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Madappa N. Kundranda
    • 1
  • Raoul Tibes
    • 1
  • Ruben A. Mesa
    • 1
  1. 1.Division of Hematology and OncologyMayo ClinicScottsdaleUSA

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