PPARγ agonists promote the resolution of myelofibrosis in preclinical models
Juliette Lambert, … , Philippe Rousselot, Stéphane Prost
Juliette Lambert, … , Philippe Rousselot, Stéphane Prost
Published April 29, 2021
Citation Information: J Clin Invest. 2021;131(11):e136713. https://doi.org/10.1172/JCI136713.
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Research Article Hematology

PPARγ agonists promote the resolution of myelofibrosis in preclinical models

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.

Authors

Juliette Lambert, Joseph Saliba, Carolina Calderon, Karine Sii-Felice, Mohammad Salma, Valérie Edmond, Jean-Claude Alvarez, Marc Delord, Caroline Marty, Isabelle Plo, Jean-Jacques Kiladjian, Eric Soler, William Vainchenker, Jean-Luc Villeval, Philippe Rousselot, Stéphane Prost

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Figure 3

Antiproliferative effect of pioglitazone on human JAK2V617F cell lines and hematopoietic progenitors from PV and MF patients.

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Antiproliferative effect of pioglitazone on human JAK2V617F cell lines a...
(A and B) Pioglitazone reduces the number of living cells in UKE-1 and HEL cell lines (n = 4) (A) and hematopoietic progenitors from a PV patient (n = 1) (B) in a dose-dependent manner. (C) Pioglitazone slightly reduces the number of living umbilical cord blood (UCB) cells (n = 3). (D and E) Pioglitazone significantly reduces the number of living cells in hematopoietic progenitors from PV patients (n = 6) (D) and hematopoietic progenitors from MF patients (n = 8) (E). (F–I) Pioglitazone reduces the clonogenic potential of UKE-1 and HEL cells (n = 3) (F), hematopoietic progenitors from UCB (G), hematopoietic progenitors from PV patients (n = 5) (H), and hematopoietic progenitors from MF patients (n = 6) (I). The black horizontal lines represent the mean. *Statistically significant difference (P < 0.05). CFC, colony-forming cell; D, day.