Journal
ONCOGENE
Volume 28, Issue 49, Pages 4364-4374Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.288
Keywords
Evi-1; Pbx1; leukemogenesis; target gene
Funding
- Japan Society for the Promotion of Science
- Health and Labour Sciences Research
- Ministry of Health, Labour and Welfare
- Grants-in-Aid for Scientific Research [19679004] Funding Source: KAKEN
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Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor, which is essential for the proliferation/maintenance of hematopoietic stem cells (HSCs). Aberrant expression of Evi-1 has been frequently found in myeloid leukemia, and is associated with a poor patient survival. Recently, we reported candidate target genes of Evi-1 shared in HSCs and leukemic cells using gene expression profiling analysis. In this study, we identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a target gene of Evi-1. Overexpression of Evi-1 increased Pbx1 expression in hematopoietic stem/progenitor cells. An analysis of the Pbx1 promoter region revealed that Evi-1 upregulates Pbx1 transcription. Furthermore, reduction of Pbx1 levels through RNAi-mediated knockdown significantly inhibited Evi-1-induced transformation. In contrast, knockdown of Pbx1 did not impair bone marrow transformation by E2A/HLF or AML1/ETO, suggesting that Pbx1 is specifically required for the maintenance of bone marrow transformation mediated by Evi-1. These results indicate that Pbx1 is a target gene of Evi-1 involved in Evi-1-mediated leukemogenesis. Oncogene (2009) 28, 4364-4374; doi: 10.1038/onc.2009.288; published online 21 September 2009
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