2. Academic Validation
  3. PPARγ agonists promote the resolution of myelofibrosis in preclinical models

PPARγ agonists promote the resolution of myelofibrosis in preclinical models

  • J Clin Invest. 2021 Jun 1;131(11):e136713. doi: 10.1172/JCI136713.
Juliette Lambert 1 2 3,  Joseph Saliba 1,  Carolina Calderon 1 3,  Karine Sii-Felice 1,  Mohammad Salma 4 5,  Valérie Edmond 6,  Jean-Claude Alvarez 7 8,  Marc Delord 9,  Caroline Marty 6,  Isabelle Plo 6,  Jean-Jacques Kiladjian 3 10,  Eric Soler 4 5,  William Vainchenker 6,  Jean-Luc Villeval 6,  Philippe Rousselot 1 2 3 11,  Stéphane Prost 1 3
Affiliations

Affiliations

  • 1 Division of Innovative Therapies, CEA/DRF/François Jacob Biology Institute, UMR1184 IMVA-HB/IDMIT, Université Paris-Saclay, Fontenay-aux-Roses, France.
  • 2 Department of Hematology and Oncology, Centre Hospitalier de Versailles, Le Chesnay, France.
  • 3 Opale Carnot Institute, Paris, France.
  • 4 Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
  • 5 Université de Paris, Laboratory of Excellence GR-Ex, Paris, France.
  • 6 INSERM, UMR1287, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
  • 7 Département de Pharmacologie-Toxicologie, Hôpitaux Universitaires Paris Ile-de-France Ouest, AP-HP, Hôpital Raymond-Poincaré, FHU Sepsis, Garches, France.
  • 8 MasSpecLab, Plateforme de spectrométrie de masse, INSERM U-1173, Université Paris-Saclay (Versailles Saint-Quentin-en-Yvelines), UFR des sciences de la santé, Montigny-le-Bretonneux, France.
  • 9 Recherche Clinique, Centre Hospitalier de Versailles, Le Chesnay, France.
  • 10 Université de Paris, AP-HP, Hôpital Saint-Louis, Centre d'Investigations Cliniques CIC 1427, INSERM, Paris, France.
  • 11 Université Paris-Saclay (Versailles Saint-Quentin-en-Yvelines), UFR des sciences de la santé, Montigny-le-Bretonneux, France.
PMID: 33914703 DOI: 10.1172/JCI136713
Abstract

Myelofibrosis (MF) is a non-BCR-ABL myeloproliferative neoplasm associated with poor outcomes. Current treatment has little effect on the natural history of the disease. MF results from complex interactions between (a) the malignant clone, (b) an inflammatory context, and (c) remodeling of the bone marrow (BM) microenvironment. Each of these points is a potential target of PPARγ activation. Here, we demonstrated the therapeutic potential of PPARγ agonists in resolving MF in 3 mouse models. We showed that PPARγ agonists reduce myeloproliferation, modulate inflammation, and protect the BM stroma in vitro and ex vivo. Activation of PPARγ constitutes a relevant therapeutic target in MF, and our data support the possibility of using PPARγ agonists in clinical practice.

Keywords

Fibrosis; Hematology; Leukemias; Stem cells.

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