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The combination of pioglitazone and imatinib is an investigational therapeutic regimen for chronic myeloid leukemia (CML), specifically evaluated in the ACTIM Phase II clinical trial sponsored by Versailles Hospital (Centre Hospitalier de Versailles). Pioglitazone, a thiazolidinedione traditionally used for type 2 diabetes, acts as a selective agonist of the peroxisome proliferator-activated receptor gamma (PPARγ). In the context of CML, pioglitazone is used as an add-on therapy to the tyrosine kinase inhibitor (TKI) imatinib to target residual disease. The mechanism involves the downregulation of STAT5 transcription, which pulls quiescent CML stem cells out of their protective dormant state and sensitizes them to the pro-apoptotic effects of imatinib. This combination aims to achieve deeper molecular responses (such as MR4.5) in patients who have achieved a major molecular response but still harbor residual leukemic clones.
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