title: The role of JAK pathway dysregulation in the pathogenesis and treatment of acute myeloid leukemia.
abstract: The discovery of the Janus kinase 2 (JAK2) V617F mutation has improved our understanding of the pathophysiology of myeloproliferative neoplasms such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Before discovery of the JAK2 V617F mutation, there were no specific targeted therapies for patients with myeloproliferative neoplasms. More recently, several small-molecule inhibitors have been developed that have shown therapeutic potential in the clinical setting. There is evidence that the JAK2 pathway is dysregulated in some acute myeloid leukemias and may also represent a novel therapeutic target in this disease. In this review, we describe the preclinical, clinical, and pathophysiologic evidence for using JAK inhibitors in the treatment of acute myeloid leukemias.
authors.affiliation: Department of Lymphoma, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000209:etiology*; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D050791:STAT Transcription Factors; D053612:Janus Kinases