Super-enhancer-driven ELOVL5 promotes T-ALL progression through the MYC-SERBP1 pathway.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with T-cell acute lymphoblastic leukemia (T-ALL) accounting for 10-25 % of cases. We identified ELOVL5 as a super-enhancer-driven oncogene that is highly expressed in T-ALL and associated with poor overall survival. Through H3K27ac ChIP-seq analysis of patient samples and cellular models, we confirmed that ELOVL5 is transcriptionally regulated by super-enhancers. Functional studies demonstrated that ELOVL5 knockdown suppressed proliferation and induced apoptosis in T-ALL cells, both in vitro and in vivo. In mouse xenograft models, silencing ELOVL5 reduced tumor burden and prolonged survival. RNA-seq analysis further revealed that ELOVL5 promotes T-ALL progression by activating MYC signaling and upregulating SERBP1, a critical downstream effector. Consistently, SERBP1 silencing also inhibited proliferation and induced apoptosis in T-ALL cells. Collectively, these findings establish ELOVL5 as a super-enhancer-associated oncogenic regulator that drives T-ALL progression through the ELOVL5-SERBP1-MYC axis, highlighting its potential as a therapeutic target.