Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development

Ming Yan, Sebastien A. Burel, Luke F. Peterson, Eiki Kanbe, Hiromi Iwasaki, Anita Boyapati, Robert Hines, Koichi Akashi, Dong Er Zhang

研究成果: Contribution to journalArticle査読

95 被引用数 (Scopus)

抄録

Normal blood-cell differentiation is controlled by regulated gene expression and signal transduction. Transcription deregulation due to chromosomal translocation is a common theme in hematopoietic neoplasms. AML1-ETO, which is a fusion protein generated by the 8;21 translocation that is commonly associated with the development of acute myeloid leukemia, fuses the AML1 runx family DNA-binding transcription factor to the ETO corepressor that associates with histone deacetylase complexes. Analyses have demonstrated that AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. Here, we report that the loss of the molecular events of AML1-ETO C-terminal NCoR/SMRT-interacting domain transforms AML1-ETO into a potent leukemogenic protein. Contrary to full-length AML1-ETO, the truncated form promotes in vitro growth and does not obstruct the cell-cycle machinery. These observations suggest a previously uncharacterized mechanism of tumorigenesis, in which secondary mutation(s) in molecular events disrupting the function of a domain of the oncogene promote the development of malignancy.

本文言語英語
ページ(範囲)17186-17191
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
101
49
DOI
出版ステータス出版済み - 12 7 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 一般

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