Collectively, these studies underscore that RARB/RARG-rearranged and KMT2A-fused APL-like leukemias represent distinct entities with unique molecular drivers, necessitating early genetic profiling to guide therapy—typically AML regimens for RARA-negative cases—while highlighting TBL1XR1-RARB as a biomarker for ATRA resistance and potential HSCT candidacy. Here, TBL1XR1 is linked to acute promyelocytic leukemia.