The P21waf1 Pathway is Involved in Blocking Leukemogenesis by the T(8;21) Fusion Protein Aml1-eto.
From: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Blood
- Publish Date: May 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 10
- Pages: 4392-8
- Medium: Print
- Language: English
- Citation (JAMA): Peterson Luke F, Yan Ming, Zhang Dong-Er, et al. The P21waf1 Pathway is Involved in Blocking Leukemogenesis by the T(8;21) Fusion Protein Aml1-eto.. Blood May 2007;109:4392-8
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.
Mesh Headings (Keywords): Animals, Cell Cycle, Chromosomes, Human, Pair 21, Chromosomes, Human, Pair 8, Core Binding Factor Alpha 2 Subunit, Cyclin-Dependent Kinase Inhibitor p21, Gene Expression Regulation, Leukemic, Humans, Jurkat Cells, K562 Cells, Leukemia, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Oncogene Proteins, Fusion, Promoter Regions (Genetics), Signal Transduction, Translocation, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 17284535
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.