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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / pathology
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Disease Models, Animal
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Hematologic Neoplasms / drug therapy*
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Hematologic Neoplasms / genetics
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Hematologic Neoplasms / metabolism
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Hematologic Neoplasms / pathology
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Mice
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Mice, Transgenic
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Neoplasm Proteins / agonists*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplasms, Experimental / drug therapy*
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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PPAR gamma / agonists*
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PPAR gamma / genetics
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PPAR gamma / metabolism
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Primary Myelofibrosis / drug therapy*
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Primary Myelofibrosis / genetics
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Primary Myelofibrosis / metabolism
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Primary Myelofibrosis / pathology
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / genetics
Substances
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Antineoplastic Agents
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Neoplasm Proteins
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PPAR gamma
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Pparg protein, mouse
Grants and funding
Etude de la pertinence thérapeutique de l’activation de PPAR<03B3> dans la prise en charge de lamyélofibrose.