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

Author:

Peterson Luke F.1,Yan Ming1,Zhang Dong-Er1

Affiliation:

1. Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA

Abstract

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 p21WAF1 gene is up-regulated by AML1-ETO at the protein, RNA, and promoter levels. Retroviral transduction and hematopoietic cell transplantation experiments with p21WAF1-deficient cells show that AML1-ETO is able to promote leukemogenesis in the absence of p21WAF1. Thus, loss of p21WAF1 facilitates AML1-ETO–induced leukemogenesis, suggesting that mutagenic events in the p21WAF1 pathway to bypass the growth inhibitory effect from AML1-ETO–induced p21WAF1 expression can be a significant factor in AML1-ETO–associated acute myeloid leukemia.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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