biostudies-literatureZhu JAssociation Laurette Fugain115-128https://www.ebi.ac.uk/biostudies/studies/S-EPMC11705203biostudies-literatureUnknown292(1)Prognosis of acute myeloid leukemia (AML) remains poor especially in older patients who are ineligible for standard chemotherapy or have refractory disease. Here, we study the potential of Peroxisome Proliferator-Activated Receptor (PPAR)-γ agonist pioglitazone to improve the treatment of AML. We show that pioglitazone exerts an anti-proliferative and anti-clonogenic effect on AML cell lines KG-1a, MOLM-14 and OCI-AML3 and on primary cultures from AML patients. However, co-culture of AML cells with stromal cells mimicking the bone marrow microenvironment counteracts this effect, suggesting the existence of a stroma-mediated resistance mechanism to pioglitazone. We show that pioglitazone treatment upregulates the receptor AXL in AML cells at the mRNA and protein level, allowing AXL to be phThe FEBS journalThe AXL inhibitor bemcentinib overcomes microenvironment-mediated resistance to pioglitazone in acute myeloid leukemia.PMC11705203ALF2016/04Calvo JZhu JGuerineau HBardet VRousselot PClauser SLefebvre-Fortane AMLargeaud LBoudouin MProst SLambert JfalseThe AXL inhibitor bemcentinib overcomes microenvironment-mediated resistance to pioglitazone in acute myeloid leukemia.Prognosis of acute myeloid leukemia (AML) remains poor especially in older patients who are ineligible for standard chemotherapy or have refractory disease. Here, we study the potential of Peroxisome Proliferator-Activated Receptor (PPAR)-γ agonist pioglitazone to improve the treatment of AML. We show that pioglitazone exerts an anti-proliferative and anti-clonogenic effect on AML cell lines KG-1a, MOLM-14 and OCI-AML3 and on primary cultures from AML patients. However, co-culture of AML cells with stromal cells mimicking the bone marrow microenvironment counteracts this effect, suggesting the existence of a stroma-mediated resistance mechanism to pioglitazone. We show that pioglitazone treatment upregulates the receptor AXL in AML cells at the mRNA and protein level, allowing AXL to be ph2025-01-01T00:00:00Z2025 Jan2026-04-08T19:03:20.85Z2025-04-04T21:48:51.536ZS-EPMC117052033932566310.1111/febs.17263