PPARγ agonists promote the resolution of myelofibrosis in preclinical models.
Animals
Antineoplastic Agents
/ pharmacology
Bone Marrow Cells
/ metabolism
Disease Models, Animal
Hematologic Neoplasms
/ drug therapy
Mice
Mice, Transgenic
Neoplasm Proteins
/ agonists
Neoplasms, Experimental
/ drug therapy
PPAR gamma
/ agonists
Primary Myelofibrosis
/ drug therapy
Tumor Microenvironment
/ drug effects
Fibrosis
Hematology
Leukemias
Stem cells
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
received:
23
01
2020
accepted:
22
04
2021
pubmed:
30
4
2021
medline:
5
10
2021
entrez:
29
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33914703
pii: 136713
doi: 10.1172/JCI136713
pmc: PMC8159700
doi:
pii:
Substances chimiques
Antineoplastic Agents
0
Neoplasm Proteins
0
PPAR gamma
0
Pparg protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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