This study integrates single-cell transcriptomic profiles of 89 B-ALL samples with normal B-cell development to map their developmental origins. It reveals that certain subtypes (BCR::ABL1, KMT2A-R, DUX4-R, ZNF384-R) resemble early multipotent progenitors, retaining myeloid potential and showing CEBPA activation. These “multipotent” leukemic states, quantified by a multipotency score, are linked to lineage plasticity and poorer survival.