Translocations involving the key B lineage transcription factors RUNX1 (ETV6-RUNX1), TCF3 (TCF3-PBX1) and EBF1 (EBF1-PDGFRβ) have all been described in human B progenitor leukemias, and deletions affecting these loci frequently occur in high-risk pediatric B-ALL.8 Our finding of greatly reduced levels of these transcription factors in EB tumors compared to late pre-B cells and cells in peripheral lymph nodes indicates that further loss of lineage-determinant transcription factors in a haploinsufficient context potentiates tumorigenesis and/or transformation. This evidence concerns the gene ETV6 and precursor B-cell acute lymphoblastic leukemia.