Among direct targets, hijacking an HLF binding site in a MYC enhancer cluster by TCF3-HLF activates a conserved MYC-driven transformation program crucial for leukemia propagation in vivo.
Since the E2A, PBX1 and HLF proteins all appear to function as transcription factors, it appears likely that the oncogenic fusion proteins contribute to leukemia development by causing abnormal transcriptional regulation of key target genes.
An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by wild-type HLF and chimeric E2A-HLF proteins isolated from various t(17;19)-bearing leukemias.