Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification [DAb-seq]
Mixed phenotype acute leukemia (MPAL) also known as acute leukemia of ambiguous lineage (ALAL), is characterized by leukemic blasts with both lymphoid and myeloid cell surface markers.   Here, we use SC multiomic profiling on newly diagnosed MPAL samples to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. This profiling allows us to definitively contradict the paradigm of MPAL as a disease on a continuum with myeloid and lymphoid lineage acute leukemias, and instead identifies MPAL as a distinct, stem-like disease that, unlike other leukemias, cannot be defined by genetics alone. We further describe a stem cell gene expression signature for MPAL that can predict patient survival. These results broaden our understanding of MPAL biology and suggest a path toward novel risk stratification for MPAL. Importantly, these findings have potential to direct treatment and, hopefully, ultimately improve the prognosis of this disease. Overall design: Samples from 14 adult patients with de novo MPAL were analyzed for single cell DNA, RNA, protein.