FUSION WITH E2A CONVERTS THE PBX1 HOMEODOMAIN PROTEIN INTO A CONSTITUTIVE TRANSCRIPTIONAL ACTIVATOR IN HUMAN LEUKEMIAS CARRYING THE T(119) TRANSLOCATION

E2A-PBX1 is a chimeric gene formed by the t(1;19)(q23;p13.3) chromosom al translocation of pediatric pre B-cell leukemia. The E2A-Pbx1 fusion protein contains sequences encoding the transactivation domain of E2A joined to a majority of the Pbx1 protein, which contains a novel home odomain. Earlier, we found that expression of E2A-Pbx1 causes malignan t transformation of NIH 3T3 fibroblasts and induces myeloid leukemia i n mice. Here we demonstrate that the homeodomains encoded by PBX1, as well as by the highly related PBX2 and PBX3 genes, bind the DNA sequen ce ATCAATCAA. E2A-Pbx1 strongly activates transcription in vivo throug h this motif, while Pbx1 does not. This finding suggests that E2A-Pbx1 transforms cells by constitutively activating transcription of genes regulated by Pbx1 or by other members of the Pbx protein family.