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However, recent studies have drawn attention towards aberrant amino acid metabolisms as actionable therapeutic targets. Here, by integrating the expression profile and genetic makeup in AML cohort, we found higher BCAT1 expression in CBF\u2010AML patients compared with other subtypes. Metabolic profiling revealed that high BCAT1 expression led to reprogrammed branch amino acid metabolism in CBF\u2010AML and was associated with sphingolipid pathway relating to the fitness of leukaemia cells, supported by transcriptomic profiling. Mechanistically, we demonstrated in cell lines and primary patient samples that BCAT1 was directly activated by RUNX1::ETO and CBF\u03b2::MYH11 fusion proteins similarly in a RUNX1\u2010dependent manner through rewiring chromatin conformation at the BCAT1 gene locus. Furthermore, BCAT1 inhibition resulted in blunted cell cycle, enhanced apoptosis and myeloid differentiation of CBF\u2010AML cells in\u00a0vitro, and alleviated leukaemia burden and prolonged survival in\u00a0vivo. Importantly, pharmacological inhibition of BCAT1 using the specific inhibitor Gabapentin demonstrated therapeutic effects, as evidenced by delayed leukaemia progression and improved survival in\u00a0vivo. In conclusion, our study uncovers BCAT1 as a genetic vulnerability and a promising targeted therapeutic opportunity for CBF\u2010AML.<\/jats:p>","DOI":"10.1111\/bjh.19565","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T19:24:51Z","timestamp":1716837891000},"page":"552-567","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RUNX1::ETO and CBF\u03b2::MYH11 converge on aberrant activation of BCAT1 to confer a therapeutic vulnerability in core\u2010binding factor\u2010acute myeloid leukaemia"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-3818","authenticated-orcid":false,"given":"Siyang","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Institute of Hematology, Ruijin Hospital Shanghai Jiao Tong University School of 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