Abstract

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 phosphatase2 (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.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.