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- Title
The E2A-HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize hematopoietic progenitors.
- Authors
de Boer, J.; Yeung, J.; Ellu, J.; Ramanujachar, R.; Bornhauser, B.; Solarska, O.; Hubank, M.; Williams, O.; Brady, H. J. M.
- Abstract
The oncogenic fusion protein E2A-HLF is a chimeric transcription factor that arises from the t(17;19) translocation in childhood B-cell acute lymphoblastic leukemias (B-precursor ALL) and is associated with very poor outcome. We show that retroviral-mediated expression of E2A-HLF alone is sufficient to immortalize primary lymphoid progenitors. We identify Lmo2 and Bcl-2 as direct target genes downstream of E2A-HLF. We use real-time PCR analysis to show that LMO2 and BCL-2 expression is preferentially upregulated both in biopsy material from t(17;19) B-precursor ALL patients and lymphoid cell lines derived from t(17;19) leukemias. Co-expression of Lmo2 and Bcl-2 was sufficient to immortalize lymphoid progenitor cells resulting in a similar phenotype to that induced by E2A-HLF alone. Both shRNA-mediated knockdown of Lmo2 expression and pharmacological inhibition of BCL-2 function in E2A-HLF immortalized cells severely compromised their viability. These data suggest that both Lmo2 and Bcl-2 are required for the action of E2A-HLF in leukemogenesis.
- Subjects
ONCOGENES; LYMPHOBLASTIC leukemia; B cells; LEUKEMIA etiology; CHROMOSOMAL translocation; GENE expression; LEUCINE zippers
- Publication
Leukemia (08876924), 2011, Vol 25, Issue 2, p321
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2010.253