The AML1/ETO fusion protein activates transcription of BCL-2

Lidija Klampfer, Jin Zhang, Andrew O. Zelenetz, Hideo Uchida, Stephen D Nimer

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

The AML1 gene, located on chromosome 21, is involved in several distinct chromosomal translocations in human leukemia. In t(8;21) acute myelogenous leukemia (AML), the AML1 gene is juxtaposed to the ETO gene located on chromosome 8, generating an AML1/ETO fusion protein. Both AML1/ETO and the AML1 proteins recognize the same consensus DNA-binding motif (TGT/CGGT), which is found in the promoters of several genes involved in hematopoiesis. We found that two myeloid leukemia cell lines with the t(8;21) translocation, Kasumi and SKNO-1, have elevated levels of BCL-2 protein compared with other myeloid cell lines. In addition, we identified a consensus AML1 binding site in the BCL-2 promoter. Thus far, AML1/ETO has been shown to dominantly repress its target genes; however, we found that AML1/ETO activates transcription of the BCL-2 gene in U937 cells. This activation requires the presence of both the runt homology domain (rhd) and the C-terminal portion of AML1/ETO. We demonstrated sequence specific binding of both AML1A and AML1/ETO to the TGTGGT sequence in the BCL-2 promoter and showed that the AML1 binding site is required for responsiveness to AML1/ETO. Interestingly, AML1A and AML1B do not modulate the activity of the BCL-2 promoter. The elevated levels of BCL-2 in cells that express AML1/ETO may prolong their life span and contribute to the development of 1(8;21) leukemia.

Original languageEnglish
Pages (from-to)14059-14064
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number24
DOIs
StatePublished - Nov 26 1996
Externally publishedYes

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Genes
Proteins
Myeloid Cells
Leukemia
Binding Sites
Cell Line
Chromosomes, Human, Pair 21
Chromosomes, Human, Pair 8
Genetic Translocation
U937 Cells
Nucleotide Motifs
Myeloid Leukemia
Hematopoiesis
Acute Myeloid Leukemia

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The AML1/ETO fusion protein activates transcription of BCL-2. / Klampfer, Lidija; Zhang, Jin; Zelenetz, Andrew O.; Uchida, Hideo; Nimer, Stephen D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 24, 26.11.1996, p. 14059-14064.

Research output: Contribution to journalArticle

Klampfer, Lidija ; Zhang, Jin ; Zelenetz, Andrew O. ; Uchida, Hideo ; Nimer, Stephen D. / The AML1/ETO fusion protein activates transcription of BCL-2. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 24. pp. 14059-14064.
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