Aberrant cytokine production by nonmalignant cells in the pathogenesis of myeloproliferative tumors and response to JAK inhibitor therapies.
نویسندگان
چکیده
Kleppe and colleagues use detailed cytokine profiling analyses to investigate the role of aberrant proinflammatory cytokine secretion in the pathogenesis of myeloproliferative neoplasms. Their analyses implicate constitutive activation of STAT3 in both malignant and nonmalignant bone marrow cell populations as a driver of aberrant cytokine secretion and as a cellular target mediating the therapeutic activity of ruxolitinib.
منابع مشابه
JAK-STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response.
UNLABELLED The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) has led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis and improves overall survival; however, the mechanism by which JAK inhibitors achieve efficacy has not been delineated. Patients with MP...
متن کامل[JAK2 inhibitors in the treatment of myeloproliferative neoplasms].
INTRODUCTION Dysregulation of JAK-STAT signaling is a pathogenetic hallmark of myeloproliferative neoplasms (MPNs) arising from several distinct molecular aberrations, including mutations in JAK2, the thrombopoietin receptor (MPL), mutations in negative regulators of JAK-STAT signaling, such as lymphocyte-specific adapter protein (SH2B3), and epigenetic dysregulation as seen with Suppressor of ...
متن کاملMolecular pathways: Jak/STAT pathway: mutations, inhibitors, and resistance.
Aberrant activation of the JAK/STAT pathway has been reported in a variety of disease states, including inflammatory conditions, hematologic malignancies, and solid tumors. For instance, a large proportion of patients with myeloproliferative neoplasms (MPN) carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of the pathogen...
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Gene expression profiling has implicated several intracellular signalling cascades, including the JAK/STAT pathway, in the pathogenesis of particular subtypes of lymphoma. In marked contrast to the situation in patients with either acute lymphoblastic leukaemia or a myeloproliferative neoplasm, JAK2 coding sequence mutations are rare in lymphoma patients with an activated JAK/STAT "signature". ...
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عنوان ژورنال:
- Cancer discovery
دوره 5 3 شماره
صفحات -
تاریخ انتشار 2015