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Type: Artigo de periódico
Title: Stathmin 1 Inhibition Amplifies Ruxolitinib-induced Apoptosis In Jak2(v617f) Cells
Author: Machado-Neto
Joao Agostinho; Campos
Paula de Melo; Favaro
Patricia; Lazarini
Mariana; Santos Duarte
Adriana da Silva; Lorand-Metze
Irene; Costa
Fernando Ferreira; Olalla Saad
Sara Teresinha; Traina
Abstract: The JAK/STAT pathway is constitutively activated in myeloproliferative neoplasms and can be inhibited by ruxolitinib, a selective JAK1/2 inhibitor. The JAK2(V617F) mutation leads to constitutive STAT3 phosphorylation and potentially leads to inhibition of Stathmin 1 activity via STAT3. In support of this hypothesis, we found that, in HEL JAK2(V617F) cells, ruxolitinib treatment decreased STAT3 and Stathmin 1 association, induced Stathmin 1 activation and microtubule instability. Silencing of Stathmin 1 significantly reduced cell proliferation and clonal growth, and increased apoptosis induced by ruxolitinib. Stathmin 1 silencing also prevented ruxolitinib-induced microtubule instability. To phenocopy the effect of Stathmin 1 inhibition, cells were treated with paclitaxel, a microtubule-stabilizing drug, in association or not with ruxolitinib; combined treatment significantly increased apoptosis, when compared to monotherapy. Notably, Stathmin 1 mRNA levels were highly expressed in CD34(+) cells from primary myelofibrosis patients. We then proposed that an undesired effect of ruxolitinib treatment may constitute Stathmin 1 activation and microtubule instability in JAK2(V617F) cells. Induction of microtubule stability, through Stathmin 1 silencing or paclitaxel treatment, combined with ruxolitinib could be an effective strategy for promoting apoptosis in JAK2(V617F) cells.
Subject: Myeloproliferative Neoplasms
Country: ALBANY
Citation: Stathmin 1 Inhibition Amplifies Ruxolitinib-induced Apoptosis In Jak2(v617f) Cells. Impact Journals Llc, v. 6, p. 29573-29584 OCT-2015.
Rights: aberto
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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