Blast Transformation in Myeloproliferative Neoplasms: Risk Factors, Biological Findings, and Targeted Therapeutic Options

Abstract

Myeloproliferative neoplasms represent a heterogenous group of disorders of the hematopoietic stem cell, with an intrinsic risk of evolution into acute myeloid leukemia. The frequency of leukemic evolution varies according to myeloproliferative neoplasms subtype. It is highest in primary myelofibrosis, where it is estimated to be approximately 10-20% at 10 years, following by polycythemia vera, with a risk of 2.3% at 10 years and 7.9% at 20 years. In essential thrombocythemia, however, transformation to acute myeloid leukemia is considered relatively uncommon. Different factors are associated with leukemic evolution in myeloproliferative neoplasms, but generally include advanced age, leukocytosis, exposure to myelosuppressive therapy, cytogenetic abnormalities, as well as increased number of mutations in genes associated with myeloid neoplasms. The prognosis of these patients is dismal, with a medium overall survival ranging from 2.6-7.0 months. Currently, there is no standard of care for managing the blast phase of these diseases, and no treatment to date has consistently led to prolonged survival and/or hematological remission apart from an allogeneic stem cell transplant. Nevertheless, new targeted agents are currently under development. In this review, we present the current evidence regarding risk factors, molecular characterization, and treatment options for this critical subset of myeloproliferative neoplasms patients.

Keywords: blast phase; mutations; myeloproliferative neoplasms; secondary acute leukemia; targeted therapies.

Figure 1

(A) Primary myelofibrosis in accelerated phase (AP). Myeloid hyperplasia with increased number of immature precursors and blasts together with large to giant megakaryocytes with hyperlobulated nuclei. (B). CD34 immunostaining highlighting the increased number of blasts and their cluster formation. (C) Paratrabecular localization of CD34-positive blasts suggests myeloproliferative neoplasm (MPN)-AP. (D) AML (M6-FAB) evolution of a case of polycythemia vera (PV). (E) Anti-E-cadherin immunostaining documenting the protein expression in the majority of acute myeloid leukemia (AML) (FAB-M6) blasts.