{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhu J"],"funding":["Association Laurette Fugain"],"pagination":["115-128"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11705203"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["292(1)"],"pubmed_abstract":["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 ph"],"journal":["The FEBS journal"],"pubmed_title":["The AXL inhibitor bemcentinib overcomes microenvironment-mediated resistance to pioglitazone in acute myeloid leukemia."],"pmcid":["PMC11705203"],"funding_grant_id":["ALF2016/04"],"pubmed_authors":["Calvo J","Zhu J","Guerineau H","Bardet V","Rousselot P","Clauser S","Lefebvre-Fortane AM","Largeaud L","Boudouin M","Prost S","Lambert J"],"additional_accession":[]},"is_claimable":false,"name":"The AXL inhibitor bemcentinib overcomes microenvironment-mediated resistance to pioglitazone in acute myeloid leukemia.","description":"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 ph","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-04-08T19:03:20.85Z","creation":"2025-04-04T21:48:51.536Z"},"accession":"S-EPMC11705203","cross_references":{"pubmed":["39325663"],"doi":["10.1111/febs.17263"]}}