The genomic and biological complexity of mixed phenotype acute leukemia

Mixed phenotype acute leukemia (MPAL) is a heterogeneous group of leukemias that are defined immunophenotypically by antigen expression on blasts of both myeloid and lymphoid lineage. With the exception of BCR-ABL positive and KMT2A rearranged MPAL, the biology of the majority of MPAL remains uncertain. Several recent studies have explored the genomic and epigenetic landscape of MPAL and have suggested a further refinement of the WHO classification to emphasize the genomic heterogeneity of MPAL. Further studies including single cell analysis, whole exome sequencing and time of flight cytometry will provide for further biological characterization. Treatment decisions are complicated due to this lack of classification and the dearth of prospective randomized studies. Acute lymphoblastic leukemia-type therapy appears to achieve higher remission rates, and allogenic stem cell transplantation may be beneficial in a select group of patients in first complete remission. Multi-center collaborations may answer these questions more conclusively. Our review aims to discuss the diagnostic challenges, recent genomic studies and therapeutic strategies in this poorly understood disease.

Automated summary

Mixed phenotype acute leukemia (MPAL) is a heterogeneous group of leukemias characterized by antigen expression on blasts of both myeloid and lymphoid lineage. While the biology of the majority of MPAL remains unclear, recent studies have started to explore the genomic and epigenetic landscape to refine the WHO classification. Treatment decisions are complicated due to lack of classification and prospective studies, with acute lymphoblastic leukemia-type therapy showing promising results and potential benefit of allogenic stem cell transplantation in certain patients. Collaborative multi-center studies may provide more conclusive answers to the questions surrounding this poorly understood disease.