title: The promise of Janus kinase inhibitors in the treatment of hematological malignancies.
abstract: The Janus kinases (JAK) are a family of kinases that play an essential role in cytokine signaling and are implicated in the pathogenesis of autoimmune diseases and hematological malignancies. As a result, the JAKs have become attractive therapeutic targets. The discovery of a JAK2 point mutation (JAK2 V617F) as the main cause of polycythemia vera lead to the development and FDA approval of a JAK1/2 inhibitor, ruxolitinib, in 2011. This review focuses on the various JAK and associated components aberrations implicated in myeloproliferative neoplasms, leukemias, and lymphomas. In addition to ruxolitinib, other JAK inhibitors are currently being evaluated in clinical trials for treating hematological malignancies. The use of JAK inhibitors alone or in combination therapy should be considered as a way to deliver targeted therapy to patients.
authors.affiliation: Cytokines and Immunity Section, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, United States.
authors.forename: Emilee
authors.initials: E
authors.lastname: Senkevitch
authors.affiliation: Cytokines and Immunity Section, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, United States. Electronic address: durums@mail.nih.gov.
authors.forename: Scott
authors.initials: S
authors.lastname: Durum
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000075242:Janus Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009196:Myeloproliferative Disorders / Q000188:drug therapy; D009570:Nitriles; D011087:Polycythemia Vera / Q000188:drug therapy; D057285:Precision Medicine; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines; D015398:Signal Transduction
chemical_list: D000075242:Janus Kinase Inhibitors; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053612:Janus Kinases
keywords: Janus kinase; Leukemia; Myeloproliferative neoplasms; Precision medicine; Ruxolitinib