Research led by St. Jude Children's Research Hospital, integrating single-cell sequencing with human hematopoietic atlases, reveals that pediatric B-cell acute lymphoblastic leukemia (B-ALL) arises from heterogeneous B-cell developmental stages. These findings, published in Nature Cancer, highlight leukemogenesis from progenitors spanning immature to differentiated states, reshaping risk stratification and therapeutic targeting. This nuanced understanding underscores the importance of cellular context in leukemia pathogenesis and may inform more precise treatment approaches.