[Tripartite fusion gene: a novel discovery in the pathogenesis and drug resistance of atypical acute promyelocytic leukemia].

Fusion genes represent a core molecular mechanism in the pathogenesis of acute promyelocytic leukemia (APL). In recent years, a novel type of tripartite retinoic acid receptor (RAR) fusion genes has been identified in atypical APL (aAPL), exhibiting distinct structural characteristics and pathogenic mechanisms compared to the classical bipartite fusion. This article systematically introduces relevant content in this field: it begins by outlining the long-standing scientific puzzle of inconsistent clinical resistance versus in vitro sensitivity in aAPL patients; subsequently, it describes the discovery process and structural features of tripartite fusion genes in all RARG and specific RARA-related cases, and elucidates the key molecular mechanism by which tripartite fusion leads to all-trans retinoic acid (ATRA) resistance at the protein conformational level; finally, the discovery of transposon involvement in the formation of tripartite fusions and its implications for the mechanism of fusion gene are discussed.