B/T mixed phenotype acute leukemia revealing immunophenotypic lineage-genotype associations and frequent myelodysplasia-related cytogenetic/gene abnormalities: implication for diagnosis and treatment.

B/T mixed-phenotype acute leukemia (MPAL) is a rare subtype of leukemia with diagnostic and therapeutic challenges due to its rarity, genomic diversity, and evolving diagnostic criteria. We report six cases of B/T MPAL with clinicopathological and genomic characterization. Most cases (5/6) demonstrated immunophenotypic/lineage-genotype-associations, i.e., T-lineage predominant B/T MPAL with T-lymphoblastic leukemia (T-ALL) genotype whereas B/T-lineage codominant B/T MPAL with combined T-ALL/B-ALL genotype. Furthermore, most patients (5/6) carried myelodysplasia-related (MR) cytogenetic-gene-alterations [MR-CG-Gene, as defined in acute myeloid leukemia (AML)-MR (AML-MR)], harboring ALL-genotype, and responded well to ALL-based induction regimens. These findings indicate that B/T MPAL with MR-CG-Gene is more appropriately diagnosed as MPAL rather than AML-MR. Our study is the first to demonstrate immunophenotypic lineage-genotype associations and frequent MR-CG-Gene in B/T MPAL and advocate more studies to refine diagnostic criteria.