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

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 () and Aurélie Thonel ()
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Margaux Sevin: University of Bourgogne Franche-Comté
Lucia Kubovcakova: University Hospital Basel
Nicolas Pernet: University of Bourgogne Franche-Comté
Sébastien Causse: University of Bourgogne Franche-Comté
Franck Vitte: Cypath
Jean Luc Villeval: Gustave Roussy
Catherine Lacout: Gustave Roussy
Marine Cordonnier: University of Bourgogne Franche-Comté
Fernando Rodrigues-Lima: CNRS UMR 8251
Gaétan Chanteloup: University of Bourgogne Franche-Comté
Matthieu Mosca: Gustave Roussy
Marie-Lorraine Chrétien: Hospital University Center (CHU)
Jean Noël Bastie: University of Bourgogne Franche-Comté
Sylvain Audia: Hospital University Center (CHU)
Paul Sagot: Hospital University Center (CHU)
Selim Ramla: Hospital University Center (CHU)
Laurent Martin: Hospital University Center (CHU)
Martin Gleave: University of British Columbia
Valérie Mezger: UMR7216 Épigénétique et Destin Cellulaire
Radek Skoda: University Hospital Basel
Isabelle Plo: Gustave Roussy
Carmen Garrido: University of Bourgogne Franche-Comté
François Girodon: University of Bourgogne Franche-Comté
Aurélie Thonel: University of Bourgogne Franche-Comté

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03627-9

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