Purpose of review
The myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera and primary myelofibrosis (PMF), are a heterogeneous group of myeloid-derived chronic haematopoietic malignancies. Frequent clinical consequences of these diseases include not only an increased risk of thrombosis but also leukemic transformation, which carries a particularly poor prognosis. Here, we discuss the recent identification of risk factors for leukemic transformation, elucidate mechanisms contributing to leukemic transformation, as well as highlight the development of new treatment strategies.
Significant progress in the understanding of the biology of MPNs has been made in recent years, particularly with the discovery that mutations in the JAK-STAT signaling pathway cause unregulated activation. These genetic insights have been extended to leukemic transformation and have revealed a host of genetic alterations that occur at the time of transformation, and that may identify patients at risk for leukemic transformation. Such studies have demonstrated that acute myeloid leukemia (AML) evolved from a chronic phase MPN is distinct from de-novo AML both genetically and clinically given its resistance to conventional antileukemic therapy.
Leukemic transformation of an MPN remains a significant clinical challenge. Recent advances in the understanding of the molecular events that contribute to the development of leukemic transformation will need to be utilized in order to produce rational therapeutic approaches for this largely fatal disease.