Lambert J, Saliba J, Calderon C, Sii-Felice K, SalmaM, Edmond V, Alvarez JC, Delord M, Marty C, Plo I, Kiladjian JJ, Soler E, Vainchenker W, Villeval JL, Rousselot P and Prost S
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2021
This study demonstrates the therapeutic potential of PPARγ agonists in treating myelofibrosis (MF), a myeloproliferative neoplasm with limited treatment options. In three mouse models, PPARγ activation reduced myeloproliferation, modulated inflammation, and preserved bone marrow stroma. These findings highlight PPARγ as a promising therapeutic target and support the clinical evaluation of PPARγ agonists in MF.
Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study.
| Rousselot P*, Prost S*, Guilhot J, Roy L, Etienne G, Legros L, Charbonnier A, CoiteuxV, Cony-Makhoul P, Huguet F, Cayssials E, Cayuela JM, Relouzat F, Delord M, Bruzzoni-Giovanelli H, Morisset L, Mahon FX, Guilhot F, Leboulch P and French CMLG (equally contributed)
| | 2017
This phase 2 clinical trial shows that adding pioglitazone, a PPARγ agonist, to imatinib therapy significantly enhances molecular response in chronic myeloid leukemia (CML) patients. After 12 months, 56% of patients progressed from major molecular response (MMR) to deep molecular response (MR4.5), compared to only 23% with imatinib alone. These findings provide clinical proof of concept for combining pioglitazone with imatinib to better target residual CML disease. |
Erosion of the chronic myeloid leukaemia stem cell pool by PPARgamma agonists.
| Prost S, Relouzat F, Spentchian M, Ouzegdouh Y, Saliba J, Massonnet G, Beressi JP, Verhoeyen E, Raggueneau V, Maneglier B, Castaigne S, Chomienne C, Chretien S, Rousselot P and Leboulch P
| | 2015
This study provides compelling evidence that glitazones, PPARγ agonists used in diabetes, can target quiescent leukemic stem cells (LSCs) in chronic myeloid leukemia (CML), which are resistant to standard tyrosine kinase inhibitor (TKI) therapy. By downregulating STAT5 and its downstream targets, glitazones disrupt LSC quiescence, enabling their eradication. In a small clinical observation, adding pioglitazone to imatinib led to sustained complete molecular responses, suggesting a promising strategy for achieving long-term CML remission. |
Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease.
| Rousselot P, Charbonnier A, Cony-Makhoul P, Agape P, Nicolini FE, Varet B, Gardembas M, Etienne G, Rea D, Roy L, Escoffre-Barbe M, Guerci-Bresler A, Tulliez M, Prost S, Spentchian M, Cayuela JM, Reiffers J, Chomel JC, Turhan A, Guilhot J, Guilhot F and Mahon FX
| | 2014
This multicenter study (A-STIM) evaluates the safety of stopping imatinib in chronic-phase CML patients with sustained complete molecular response (CMR). Results show that 64% of patients maintained treatment-free remission at 12 and 24 months, and that loss of major molecular response (MMR) is a reliable and safe criterion to resume therapy. Reintroduction of imatinib led to rapid recovery of CMR, supporting a more flexible, individualized approach to treatment discontinuation. |
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