Navigating the Grey Zone: A Series of Three Cases on Mixed-phenotype Acute Leukaemia

Mixed-phenotype Acute leukaemia (MPAL) may consist of a single population of abnormal progenitors (morphological blasts) expressing antigens from two or more lineages. MPAL remains one of the most diagnostically challenging groups of acute leukaemias because of its intrinsic biological heterogeneity and overlap with both Acute Myeloid Leukaemia (AML) and Acute Lymphoblastic Leukaemia (ALL). Lineage assignment is best performed by Flow Cytometric Immunophenotyping (FCM IPT) in order to correlate the patterns of antigen expression on one or more cell populations. Authors present three cases of mixed phenotype acute leukaemia to highlight the breadth of MPAL presentations across age groups, ranging from neonates to elderly adults. Case 1 was of a 62-year-old male diagnosed with B/Myeloid MPAL whose molecular analysis revealed IDH2, SRSF2, and CUX1 mutations with del(7q), suggesting evolution from a myeloid clonal background. The high VAF of CUX1 (77.39%) in the context of del(7q) likely indicates Loss Of Heterozygosity (LOH). Case 2 (64-year-old male) presented with Central Nervous System (CNS) infiltration. In Case 3, 85-day-old male infant with B/T MPAL presented with extreme hyperleukocytosis and rapid clinical deterioration. This series underscores the marked biological and clinical heterogeneity of MPAL across age groups and disease subtypes, reinforces the critical role of multiparameter flow cytometry in objective lineage assignment, and highlights the importance of integrating immunophenotypic, cytogenetic, and molecular data to establish an accurate diagnosis. The varied clinical courses observed also reflect the prognostic unpredictability of MPAL and the practical challenges of managing this rare entity, particularly in resourcelimited settings, emphasising the need for early recognition and comprehensive diagnostic evaluation to guide optimal therapy.