Direct and Indirect Targets of the E2A-PBX1 Leukemia-Specific Fusion Protein

摘要: E2A-PBX1 is expressed as a result of the t(1;19) chromosomal translocation in nearly 5% cases childhood acute lymphoblastic leukemia. The chimeric transcription factor contains N-terminal transactivation domain E2A (TCF3) fused to C-terminal DNA-binding homeodomain PBX1. While there no doubt its oncogenic potential, mechanisms E2A-PBX1-mediated pre-B cell transformation and nature direct target genes pathways remain largely unknown. Herein we used chromatin immunoprecipitation assays (ChIP-chip) identify targets E2A-PBX1, gene expression arrays siRNA E2A-PBX1-silenced cells evaluate changes induced by fusion protein. Combined ChIP-chip data analysis gave rise functional E2A-PBX1. Further observe that set identified show collective down-regulation trend silenced samples compared controls suggesting an activating role this factor. Our suggest interferes with key regulatory functions hematopoietic biology. Among these are members WNT apoptosis/cell cycle control pathways, thus may comprise essential driving force for propagation maintenance leukemic phenotype. These findings also provide evidence potentially attractive therapeutic targets.