Article

The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO.

Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Blood (Impact Factor: 9.78). 06/2007; 109(10):4392-8. DOI: 10.1182/blood-2006-03-012575
Source: PubMed

ABSTRACT The 8;21 translocation is a major contributor to acute myeloid leukemia (AML) of the M2 classification occurring in approximately 40% of these cases. Multiple mouse models using this fusion protein demonstrate that AML1-ETO requires secondary mutagenic events to promote leukemogenesis. Here, we show that the negative cell cycle regulator p21(WAF1) gene is up-regulated by AML1-ETO at the protein, RNA, and promoter levels. Retroviral transduction and hematopoietic cell transplantation experiments with p21(WAF1)-deficient cells show that AML1-ETO is able to promote leukemogenesis in the absence of p21(WAF1). Thus, loss of p21(WAF1) facilitates AML1-ETO-induced leukemogenesis, suggesting that mutagenic events in the p21(WAF1) pathway to bypass the growth inhibitory effect from AML1-ETO-induced p21(WAF1) expression can be a significant factor in AML1-ETO-associated acute myeloid leukemia.

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