Merck

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

Nature communications (2018-04-14)
Margaux Sevin, Lucia Kubovcakova, Nicolas Pernet, Sébastien Causse, Franck Vitte, Jean Luc Villeval, Catherine Lacout, Marine Cordonnier, Fernando Rodrigues-Lima, Gaétan Chanteloup, Matthieu Mosca, Marie-Lorraine Chrétien, Jean Noël Bastie, Sylvain Audia, Paul Sagot, Selim Ramla, Laurent Martin, Martin Gleave, Valérie Mezger, Radek Skoda, Isabelle Plo, Carmen Garrido, François Girodon, Aurélie de Thonel
RESUMEN

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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