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; Aurélie De Thonel

doi:10.1038/s41467-018-03627-9

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 SkodaIsabelle Plo, Carmen Garrido, François Girodon, Aurélie De Thonel

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

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.

Original language	English
Article number	1431
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-03627-9
Publication status	Published - 1 Dec 2018

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Sevin, M., Kubovcakova, L., Pernet, N., Causse, S., Vitte, F., Villeval, J. L., Lacout, C., Cordonnier, M., Rodrigues-Lima, F., Chanteloup, G., Mosca, M., Chrétien, M. L., Bastie, J. N., Audia, S., Sagot, P., Ramla, S., Martin, L., Gleave, M., Mezger, V., ... De Thonel, A. (2018). HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis. Nature Communications, 9(1), Article 1431. https://doi.org/10.1038/s41467-018-03627-9

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title = "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.",

author = "Margaux Sevin and Lucia Kubovcakova and Nicolas Pernet and S{\'e}bastien Causse and Franck Vitte and Villeval, {Jean Luc} and Catherine Lacout and Marine Cordonnier and Fernando Rodrigues-Lima and Ga{\'e}tan Chanteloup and Matthieu Mosca and Chr{\'e}tien, {Marie Lorraine} and Bastie, {Jean No{\"e}l} and Sylvain Audia and Paul Sagot and Selim Ramla and Laurent Martin and Martin Gleave and Val{\'e}rie Mezger and Radek Skoda and Isabelle Plo and Carmen Garrido and Fran{\c c}ois Girodon and {De Thonel}, Aur{\'e}lie",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

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doi = "10.1038/s41467-018-03627-9",

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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 2018, 'HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis', Nature Communications, vol. 9, no. 1, 1431. https://doi.org/10.1038/s41467-018-03627-9

TY - JOUR

T1 - HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis

AU - Sevin, Margaux

AU - Kubovcakova, Lucia

AU - Pernet, Nicolas

AU - Causse, Sébastien

AU - Vitte, Franck

AU - Villeval, Jean Luc

AU - Lacout, Catherine

AU - Cordonnier, Marine

AU - Rodrigues-Lima, Fernando

AU - Chanteloup, Gaétan

AU - Mosca, Matthieu

AU - Chrétien, Marie Lorraine

AU - Bastie, Jean Noël

AU - Audia, Sylvain

AU - Sagot, Paul

AU - Ramla, Selim

AU - Martin, Laurent

AU - Gleave, Martin

AU - Mezger, Valérie

AU - Skoda, Radek

AU - Plo, Isabelle

AU - Garrido, Carmen

AU - Girodon, François

AU - De Thonel, Aurélie

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85045520545&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-03627-9

DO - 10.1038/s41467-018-03627-9

M3 - Article

C2 - 29650953

AN - SCOPUS:85045520545

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1431

ER -

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

Abstract

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