JAK-mutant myeloproliferative neoplasms Journal Article
| Author: | Levine, R. L. |
| Article Title: | JAK-mutant myeloproliferative neoplasms |
| Abstract: | Although the Janus family of kinases (JAK1, JAK2, JAK3, and TYK2) has been extensively characterized and investigated, the role of Janus kinase activation in the pathogenesis and therapy of human malignancies was not fully appreciated until recently when multiple studies identified a recurrent somatic mutation in the JAK2 tyrosine kinase (JAK2V617F) in the majority of patients with BCR-ABL-negative myeloproliferative neoplasms (MPN), polycythemia vera, essential thrombocytosis, and primary myelofibrosis. Other mutations that activate the JAK-STAT signaling pathway have since been identified in JAK2V617F-negative MPN patients and in a subset of patients with acute myeloid leukemia and acute lymphoid leukemia. In addition, dysregulated JAK-STAT signaling has been implicated in the pathogenesis of a spectrum of epithelial neoplasms. In this chapter, we will review the recent studies that identified genetic alterations that activate JAK signaling in different malignancies, and discuss the recent efforts aimed at developing small-molecule inhibitors of JAK kinase activity for the treatment of MPNs and other malignancies. © 2012 Springer-Verlag Berlin Heidelberg. |
| Keywords: | myelofibrosis; unclassified drug; acute granulocytic leukemia; somatic mutation; missense mutation; janus kinase 2; janus kinase inhibitor; myeloid metaplasia; nonhuman; neurotoxicity; gene; anemia; thrombocytopenia; chronic myeloid leukemia; acute lymphoblastic leukemia; protein tyrosine kinase inhibitor; homozygosity; uniparental disomy; guanine; janus kinase; protein kinase tyk2; point mutation; malignant transformation; genetic predisposition; loss of function mutation; myeloproliferative neoplasm; thymidine; polycythemia vera; tet2 gene; stat protein; bone marrow depression; janus kinase 2 inhibitor; nucleic acid base substitution; janus kinase 1; janus kinase 3; cancer prognosis; 5 chloro n2 [1 (5 fluoro 2 pyrimidinyl)ethyl] n4 (5 methyl 1h pyrazol 3 yl) 2,4 pyrimidinediamine; n tert butyl 3 [5 methyl 2 [4 [2 (1 pyrrolidinyl)ethoxy]phenylamino] 4 pyrimidinylamino]benzenesulfonamide; ruxolitinib; essential thrombocytosis; cyt 787; exl 019 |
| Journal Title: | Current Topics in Microbiology and Immunology |
| Volume: | 355 |
| ISSN: | 0070-217X |
| Publisher: | Springer Verlag |
| Date Published: | 2012-01-01 |
| Start Page: | 119 |
| End Page: | 133 |
| Language: | English |
| DOI: | 10.1007/82_2011_170 |
| PROVIDER: | scopus |
| PUBMED: | 21823028 |
| DOI/URL: | |
| Notes: | In "Therapeutic Kinase Inhibitors" (ISBN: 978-3-642-28295-9) -- "Cited By (since 1996): 1" - "Export Date: 1 February 2013" - "CODEN: CTMIA" - "Source: Scopus" |
