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

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Listed:
  • Margaux Sevin

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer)

  • Lucia Kubovcakova

    (University Hospital Basel)

  • Nicolas Pernet

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer)

  • Sébastien Causse

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer)

  • Franck Vitte

    (Cypath)

  • Jean Luc Villeval

    (Gustave Roussy
    Laboratory of Excellence GR-Ex)

  • Catherine Lacout

    (Gustave Roussy
    Laboratory of Excellence GR-Ex)

  • Marine Cordonnier

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer)

  • Fernando Rodrigues-Lima

    (CNRS UMR 8251)

  • Gaétan Chanteloup

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer)

  • Matthieu Mosca

    (Gustave Roussy
    Laboratory of Excellence GR-Ex)

  • Marie-Lorraine Chrétien

    (Hospital University Center (CHU))

  • Jean Noël Bastie

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer
    Hospital University Center (CHU))

  • 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
    Sorbonne Paris Cité
    Département Hospitalo-Universitaire DHU PROTECT)

  • Radek Skoda

    (University Hospital Basel)

  • Isabelle Plo

    (Gustave Roussy
    Laboratory of Excellence GR-Ex)

  • Carmen Garrido

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer
    Centre Georges François Leclerc (CGFL)
    LipSTIC LabEx)

  • François Girodon

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer
    Hospital University Center (CHU))

  • Aurélie Thonel

    (University of Bourgogne Franche-Comté
    UMR 1231, Laboratory of Excellence Ligue National contre le Cancer
    UMR7216 Épigénétique et Destin Cellulaire
    Sorbonne Paris Cité)

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.

Suggested Citation

  • Margaux Sevin & Lucia Kubovcakova & Nicolas Pernet & Sébastien Causse & Franck Vitte & Jean Luc Villeval & Catherine Lacout & Marine Cordonnier & Fernando Rodrigues-Lima & Gaétan Chanteloup & Matthieu, 2018. "HSP27 is a partner of JAK2-STAT5 and a potential therapeutic target in myelofibrosis," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03627-9
    DOI: 10.1038/s41467-018-03627-9
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