The immunoglobulin enhancer‑binding factor/hepatic leukemia factor (E2A‑HLF) oncogenic fusion gene, generated by t(17;19)(q22;p13) translocation in childhood B‑cell acute lymphoblastic leukemia with a very poor prognosis, encodes a chimeric transcription factor in which the transactivation domains of E2A are fused to the DNA‑binding and dimerization domain of HLF. E2A‑HLF has been demonstrated to have an anti‑apoptotic effect. However, the molecular mechanism underlying E2A‑HLF‑mediated leukemogenesis remains unclear. The present study identified EYA transcriptional coactivator and phosphatase 2 (Eya2), the forced expression of which is known to immortalize mouse hematopoietic stem/progenitor cells (HSPCs), as a direct target molecule downstream of E2A‑HLF. E2A‑HLF‑immortalized mouse HSPCs expressed Eya2 at a high level in the aberrant self‑renewal program. Chromatin immunoprecipitation‑quantitative polymerase chain reaction and a reporter assay revealed that E2A‑HLF enhanced the Eya2 expression by binding to the promoter region containing the E2A‑HLF‑binding consensus sequence. Eya2 knockdown in E2A‑HLF‑immortalized cells resulted in reduced colony‑forming efficiency. These results suggest a critical role of Eya2 in E2A‑HLF‑mediated leukemogenesis.
Keywords: EYA transcriptional coactivator and phosphatase 2; immunoglobulin enhancer-binding factor/hepatic leukemia factor; leukemia; self-renewal; immortalization.