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JAK-Mutant Myeloproliferative Neoplasms

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Therapeutic Kinase Inhibitors

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 355))

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.

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Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, New York, NY, 10021, USA

    Ross L. Levine

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  1. Ross L. Levine
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Correspondence to Ross L. Levine .

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  1. , Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, York Avenue 1275, New York, 10065, New York, USA

    Ingo K. Mellinghoff

  2. , Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, York Avenue 1275, New York, 10065, New York, USA

    Charles L. Sawyers

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Levine, R.L. (2011). JAK-Mutant Myeloproliferative Neoplasms. In: Mellinghoff, I., Sawyers, C. (eds) Therapeutic Kinase Inhibitors. Current Topics in Microbiology and Immunology, vol 355. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_170

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