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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)17186-17191
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number49
DOIs
Publication statusPublished - Dec 7 2004

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Leukemia
Co-Repressor Proteins
Genetic Translocation
Histone Deacetylases
Hematologic Neoplasms
Oncogenes
Acute Myeloid Leukemia
Cell Differentiation
Signal Transduction
Blood Cells
Cell Cycle
Carcinogenesis
Proteins
Transcription Factors
Gene Expression
Mutation
DNA
Growth
Neoplasms
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • General

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Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development. / Yan, Ming; Burel, Sebastien A.; Peterson, Luke F.; Kanbe, Eiki; Iwasaki, Hiromi; Boyapati, Anita; Hines, Robert; Akashi, Koichi; Zhang, Dong Er.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 49, 07.12.2004, p. 17186-17191.

Research output: Contribution to journalArticle

Yan, Ming ; Burel, Sebastien A. ; Peterson, Luke F. ; Kanbe, Eiki ; Iwasaki, Hiromi ; Boyapati, Anita ; Hines, Robert ; Akashi, Koichi ; Zhang, Dong Er. / Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 49. pp. 17186-17191.
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AU - Burel, Sebastien A.

AU - Peterson, Luke F.

AU - Kanbe, Eiki

AU - Iwasaki, Hiromi

AU - Boyapati, Anita

AU - Hines, Robert

AU - Akashi, Koichi

AU - Zhang, Dong Er

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