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PMID: 7972130 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Growth inhibition and induction of differentiation of t(8;21) acute myeloid leukemia cells by the DNA-binding domain of PEBP2 and the AML1/MTG8(ETO)-specific antisense oligonucleotide.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 24 ·1994-11-22 ·Pages 11723-7

Sakakura C, Yamaguchi-Iwai Y, Satake M, Bae SC, Takahashi A, Ogawa E, Hagiwara A, Takahashi T, Murakami A, Makino K

Abstract

The translocation from chromosome 8 to chromosome 21, t(8;21), associated with acute myeloid leukemia results in production of an AML1/MTG8(ETO) fusion transcript. The product of the AML1 gene contains an evolutionarily conserved 128-amino acid region referred to as the "Runt domain," which is necessary for binding to DNA at the PEBP2 site. A fragment of the AML1 protein containing mainly the Runt domain and the antisense oligonucleotide complementary to the fusion transcript strongly inhibited the growth and induced differentiation of cell lines derived from acute myeloid leukemia containing t(8;21). These results indicate that the transcriptional regulation through the PEBP2 site is critically important for growth and differentiation of t(8;21) leukemic cells and that the product of the chimeric gene is responsible for the maintenance of the leukemic phenotype.

Related Genes
AML1 ETO MTG8 PEBP2
MeSH Terms
Acute Disease Base Sequence Binding, Competitive Cell Differentiation Chromosomes, Human, Pair 21 Chromosomes, Human, Pair 8 DNA-Binding Proteins/physiology Gene Expression Growth Inhibitors Humans Leukemia, Myeloid/genetics,pathology Molecular Sequence Data Oligonucleotides, Antisense/chemistry Proto-Oncogene Proteins RNA, Messenger/genetics RUNX1 Translocation Partner 1 Protein Recombinant Fusion Proteins Transcription Factor AP-2 Transcription Factors/physiology Translocation, Genetic
Chemicals
DNA-Binding Proteins Growth Inhibitors Oligonucleotides, Antisense Proto-Oncogene Proteins RNA, Messenger RUNX1 Translocation Partner 1 Protein RUNX1T1 protein, human Recombinant Fusion Proteins Transcription Factor AP-2 Transcription Factors
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Sakakura C
Department of Viral Oncology, Kyoto University, Japan.
Yamaguchi-Iwai Y
Satake M
Bae S C
Takahashi A
Ogawa E
Hagiwara A
Takahashi T
Murakami A
Makino K
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32 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.24.11723
Published
1994-11-22
Pages
11723-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC45304
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.91.24.11723 PMC Full Text View journal details
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