A study published in Nature Cancer has revealed that the developmental stage of B cells at leukemia onset critically affects therapy response in pediatric B-cell acute lymphoblastic leukemia (B-ALL). By mapping leukemic cells to a detailed single-cell atlas of normal human B-cell differentiation, researchers identified heterogeneity in malignant origins ranging from early progenitors to mature cells. This nuanced understanding challenges existing paradigms and suggests tailored treatment approaches based on cellular ontogeny may improve patient outcomes. The work leverages collaborations at St. Jude Children’s Research Hospital and University Health Network's Princess Margaret Cancer Centre.