HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis.
Fiche publication
Date publication
avril 2018
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BASTIE Jean-Noël, Dr GARRIDO Carmen, Pr MARTIN Laurent, Pr GIRODON François, Dr CHRETIEN Marie-Lorraine , Mr PERNET Nicolas
Tous les auteurs :
Sevin M, Kubovcakova L, Pernet N, Causse S, Vitte F, Villeval JL, Lacout C, Cordonnier M, Rodrigues-Lima F, Chanteloup G, Mosca M, Chrétien ML, Bastie JN, Audia S, Sagot P, Ramla S, Martin L, Gleave M, Mezger V, Skoda R, Plo I, Garrido C, Girodon F, de Thonel A
Lien Pubmed
Résumé
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.
Mots clés
Animals, Bone Marrow Cells, immunology, Bone Marrow Transplantation, Cell Line, Tumor, Disease Models, Animal, Female, HEK293 Cells, HSP27 Heat-Shock Proteins, genetics, Humans, Janus Kinase 2, genetics, K562 Cells, Leukocytes, drug effects, Mice, Mice, Inbred C57BL, Mice, Transgenic, Molecular Targeted Therapy, Mutation, Oligonucleotides, pharmacology, Primary Myelofibrosis, drug therapy, STAT5 Transcription Factor, genetics, Thrombopoietin, genetics, Transduction, Genetic, Whole-Body Irradiation
Référence
Nat Commun. 2018 Apr 12;9(1):1431