Fusion with E2A alters the transcriptional properties of the homeodomain protein PBX1 in t(1;19) leukemias.

The t(1;19) chromosomal translocation is observed in pre-B cell acute lymphoblastic leukemias and results in expression of chimeric E2A-PBX1 proteins that contain transcriptional activation domains from E2A and the homeodomain of PBX1. Since homeodomains mediate DNA-binding, a potential model for the action of E2A-PBXI is that it disrupts the transcriptional regulation of genes normally controlled by PBX1 or its closely-related family members PBX2 or PBX3. Using a binding site selection assay, we identified a consensus nucleotide sequence ATCAATCA specifically bound by the PBX1 homeodomain and those of its closely-related family members PBX2 and PBX3