JAK2 Mutants (e.g., JAK2V617F) and Their Importance As Drug Targets in Myeloproliferative Neoplasms

Overview

Journal JAKSTAT

Date 2013 Sep 27

PMID 24069563

Citations 20

Authors

Karoline Gabler

Iris Behrmann

Claude Haan

Affiliations

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Abstract

The Janus kinase 2 (JAK2) mutant V617F and other JAK mutants are found in patients with myeloproliferative neoplasms and leukemias. Due to their involvement in neoplasia and inflammatory disorders, Janus kinases are promising targets for kinase inhibitor therapy. Several small-molecule compounds are evaluated in clinical trials for myelofibrosis, and ruxolitinib (INCB018424, Jakafi®) was the first Janus kinase inhibitor to receive clinical approval. In this review we provide an overview of JAK2V617F signaling and its inhibition by small-molecule kinase inhibitors. In addition, myeloproliferative neoplasms are discussed regarding the role of JAK2V617F and other mutant proteins of possible relevance. We further give an overview about treatment options with special emphasis on possible combination therapies.

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