Adult mixed phenotype acute leukemia (MPAL): B/myeloid MPAL^isoMPO is distinct from other MPAL subtypes

Introduction: Myeloperoxidase (MPO) is considered a specific marker of myeloid/non-monocytic lineage in the diagnosis of mixed phenotype acute leukemia (MPAL). However, the clinical significance of isolated dim MPO expression in otherwise typical B lymphoblastic leukemia (B-ALL; referred to as B/myeloid MPAL^isoMPO) in adult patients is unknown. Methods: We compared flow cytometric immunophenotype and clinicopathological findings among cases of B/myeloid MPAL^isoMPO (n = 13), other MPAL subtypes (n = 10, B/myeloid and T/myeloid MPAL), B-ALL (n = 64), and acute myeloid leukemia (AML, n = 58), using the 2016 WHO classification. For MPAL cases, MPO was reported as the percent of MPO positive blasts and its intensity (dim or moderate/strong). The pattern of heterogenous antigen expression (inversely coordinated expression between myeloid and lymphoid markers and cell size) was assessed. Results: Cases of B/myeloid MPAL^isoMPO showed a fairly homogenous single B-lineage blast population with dim MPO expression whereas cases of other MPAL subtypes displayed heterogeneous antigen expression and moderate/strong MPO expression. The percent of MPO positive blasts in these two groups was similar. Expressions of CD15, CD117, and monocytic markers were more common in other MPAL than in B/myeloid MPAL^isoMPO. B/myeloid MPAL^isoMPO patients had similar overall and leukemia free survivals as B-ALL patients and better than other MPAL patients. Conclusion: This is the first study to investigate the clinical significance of adult B/myeloid MPAL^isoMPO using the 2016 WHO classification. Our results suggest that B/myeloid MPAL^isoMPO clinically behaves more similarly to B-ALL than to other MPAL subtypes, supporting the 2016 WHO classification to segregate this entity from other MPAL subtypes.