Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells

Purpose: Metabolic reprogramming is a key feature of cellular transformation. Although the mitochondrial genome encodes components of the electron transport chain that produce tumor-modifying metabolic signals, the contribution of somatic mtDNA mutations in cancer pathophysiology remains unclear. Here, we employed scRNA-seq to capture cell state changes associated with pathogenic, tumor-enriched mtDNA variants in primary leukemic blasts using single-cell RNA sequencing (scRNA-seq) Single-cell RNA sequencing (Chromium, 10X Genomics) of three B-ALL tumor samples that were positive for the t(1;19)(q23;p13) translocation (TCF3-PBX1+/E2A-PBX1+)