Mixed phenotype acute leukemia, the dissection of an enigmatic disease in the era of novel therapies.

Background: Mixed-phenotype acute leukemia (MPAL) is a rare and heterogeneous subtype of acute leukemia, associated with unfavorable outcomes. MPAL is defined by the presence of more than 20% blasts and bi- or trilineage assignment based on strong immunophenotypic markers, with specific subcategories characterized by Methods: Data were synthesized primarily from meta-analyses and original studies, with a particular emphasis on the roles of immunophenotyping, cytogenetics, and novel targeted therapies from 1985 to the present. Results: MPAL accounts for 1%-5% of acute leukemias, with B/myeloid (59%) and T/myeloid (35%) subtypes being the most prevalent. Cytogenetic abnormalities are identified in up to 90% of cases, predominantly complex karyotypes. Molecular investigations have identified frequent mutations in genes such as Conclusions: MPAL remains a significant challenge in diagnosis and treatment. Advances in molecular characterization have enhanced classification techniques and have the potential to inform personalized treatment strategies. Considering the rarity and heterogeneity of MPAL, extensive prospective multicenter trials are imperative to develop evidence-based therapeutic protocols.