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HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis

Abstract : Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that facilitates cancer development by its proliferative and anti-apoptotic functions. The OGX-427 antisense oligonucleotide against HSP27 has been reported to be beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is effective in two murine models of thrombopoietin- and JAKV617F-induced myelofibrosis. OGX-427 limits disease progression and is associated with a reduction in spleen weight, in megakaryocyte expansion and, for the JAKV617F model, in fibrosis. HSP27 regulates the proliferation of JAK2V617F-positive cells and interacts directly with JAK2/STAT5. We also show that its expression is increased in both CD34+ circulating progenitors and in the serum of patients with JAK2-dependent myeloproliferative neoplasms with fibrosis. Our data suggest that HSP27 plays a key role in the pathophysiology of myelofibrosis and represents a new potential therapeutic target for patients with myeloproliferative neoplasms.
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Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 29 août 2018 - 16:11:13
Dernière modification le : vendredi 18 septembre 2020 - 14:34:59

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Margaux Sevin, Lucia Kubovcakova, Nicolas Pernet, Sebastien Causse, Franck Vitte, et al.. HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis. Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.1431. ⟨10.1038/s41467-018-03627-9⟩. ⟨hal-01864299⟩



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