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

Chouhei Sakakura, Yuko Yamaguchi-Iwai, Masanobu Satake, Suk Chul Bae, Atsushi Takahashi, Eiko Ogawa, Akeo Hagiwara, Toshio Takahashi, Akira Murakami, Keisuke Makino, Toshitaro Nakagawa, Nanao Kamada, Yoshiaki Ito

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92 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11723-11727
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number24
DOIs
Publication statusPublished - 1994 Nov 22

ASJC Scopus subject areas

  • General

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