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Pathogenesis and management of acute myeloid leukemia that has evolved from a myeloproliferative neoplasm

Rampal, Raajita; Mascarenhas, Johnb

Current Opinion in Hematology: March 2014 - Volume 21 - Issue 2 - p 65–71
doi: 10.1097/MOH.0000000000000017
MYELOID DISEASE: Edited by Martin S. Tallman

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.

Recent findings 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.

Summary 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.

aLeukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center

bTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Correspondence to Raajit Rampal, MD, PhD, Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 443 New York, NY 10065, USA. Tel: +1 212 639 2194; fax: +1 212 772 8550; email:

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins