biostudies-literatureShen YGShanghai Science and Technology Commission's Explorer Programthe National Key R&D Program of Chinathe National Natural Science Foundation of Chinathe Clinical Research Plan of Shanghai Hospital Development Center137https://www.ebi.ac.uk/biostudies/studies/S-EPMC12690028biostudies-literatureUnknown6(1)High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements constitutes a distinct clinicopathological entity characterized by aggressive behavior, inherent resistance to conventional immunochemotherapy, and suboptimal clinical outcomes. Within our cohort, MYC/BCL2 rearrangements defined double-hit lymphoma (DHL), MYC/BCL6 as DHL-BCL6, and concurrent MYC/BCL2/BCL6 as triple-hit lymphoma (THL). Here, we delineated the clinical characteristics and genetic aberrations of 112 DHL/THL patients to investigate the factors influencing lymphoma relapse and optimize treatment strategies. Compared to 80 DHL-BCL6 patients, DHL/THL manifested distinct features, including an increased prevalence of the germinal center B-cell-like subtype and co-expression of MYC/BCL2, and demonstrated signifMolecular biomedicineClinicopathological characteristics, genetic aberrations, and optimized treatment strategies in double-hit and triple-hit lymphoma: a multi-center cohort study.PMC1269002882170178825702462022YFC250260025TS1404000SHDC2020CR1032B82130004822002012023YFC3605704Ji MMWang XBShi QHuang LZhao WLWei XLShen YGLiang ABZhu ZMWang LCheng SLiu YBai OXu BFan LWang XTang WZhou HZheng ZHuang HHShi WYYi HMChen SYLi FXu PPDong LHYang SMLiu TBShi KQTian YYfalseClinicopathological characteristics, genetic aberrations, and optimized treatment strategies in double-hit and triple-hit lymphoma: a multi-center cohort study.High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements constitutes a distinct clinicopathological entity characterized by aggressive behavior, inherent resistance to conventional immunochemotherapy, and suboptimal clinical outcomes. Within our cohort, MYC/BCL2 rearrangements defined double-hit lymphoma (DHL), MYC/BCL6 as DHL-BCL6, and concurrent MYC/BCL2/BCL6 as triple-hit lymphoma (THL). Here, we delineated the clinical characteristics and genetic aberrations of 112 DHL/THL patients to investigate the factors influencing lymphoma relapse and optimize treatment strategies. Compared to 80 DHL-BCL6 patients, DHL/THL manifested distinct features, including an increased prevalence of the germinal center B-cell-like subtype and co-expression of MYC/BCL2, and demonstrated signif2025-01-01T00:00:00Z2025 Dec2026-06-06T00:07:59.65Z2026-05-23T03:13:40.461ZS-EPMC126900284136430510.1186/s43556-025-00346-8