{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hoang NM"],"funding":["NCI NIH HHS","National Institutes of Health"],"pagination":["101484"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11031386"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(4)"],"pubmed_abstract":["The use of Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib achieves a remarkable clinical response in mantle cell lymphoma (MCL). Acquired drug resistance, however, is significant and affects long-term survival of MCL patients. Here, we demonstrate that DNA methyltransferase 3A (DNMT3A) is involved in ibrutinib resistance. We find that DNMT3A expression is upregulated upon ibrutinib treatment in ibrutinib-resistant MCL cells. Genetic and pharmacological analyses reveal that DNMT3A mediates ibrutinib resistance independent of its DNA-methylation function. Mechanistically, DNMT3A induces the expression of MYC target genes through interaction with the transcription factors MEF2B and MYC, thus mediating metabolic reprogramming to oxidative phosphorylation (OXPHOS). Targeting DNMT3A with low-dose decitabine inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting DNMT3A-mediated metabolic reprogramming to OXPHOS with decitabine provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory MCL."],"journal":["Cell reports. Medicine"],"pubmed_title":["Targeting DNMT3A-mediated oxidative phosphorylation to overcome ibrutinib resistance in mantle cell lymphoma."],"pmcid":["PMC11031386"],"funding_grant_id":["R01 CA266354","P30 CA014520","R01 CA272855"],"pubmed_authors":["Selberg PE","Kondapelli A","Hoang NM","Liu P","Zhu F","Rui L","Lopez AF","Liu Y","Bates PD","Heaton AR","Zhang X","Skala MC","Ngo VN","Capitini CM","Chen R"],"additional_accession":[]},"is_claimable":false,"name":"Targeting DNMT3A-mediated oxidative phosphorylation to overcome ibrutinib resistance in mantle cell lymphoma.","description":"The use of Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib achieves a remarkable clinical response in mantle cell lymphoma (MCL). Acquired drug resistance, however, is significant and affects long-term survival of MCL patients. Here, we demonstrate that DNA methyltransferase 3A (DNMT3A) is involved in ibrutinib resistance. We find that DNMT3A expression is upregulated upon ibrutinib treatment in ibrutinib-resistant MCL cells. Genetic and pharmacological analyses reveal that DNMT3A mediates ibrutinib resistance independent of its DNA-methylation function. Mechanistically, DNMT3A induces the expression of MYC target genes through interaction with the transcription factors MEF2B and MYC, thus mediating metabolic reprogramming to oxidative phosphorylation (OXPHOS). Targeting DNMT3A with low-dose decitabine inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting DNMT3A-mediated metabolic reprogramming to OXPHOS with decitabine provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory MCL.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T23:47:49.521Z","creation":"2026-05-23T03:08:09.394Z"},"accession":"S-EPMC11031386","cross_references":{"pubmed":["38554704"],"doi":["10.1016/j.xcrm.2024.101484"]}}