Sakakura C, Yamaguchi-Iwai Y, Satake M, Bae S C, Takahashi A, Ogawa E, Hagiwara A, Takahashi T, Murakami A, Makino K
Department of Viral Oncology, Kyoto University, Japan.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11723-7. doi: 10.1073/pnas.91.24.11723.
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.
与急性髓系白血病相关的8号染色体与21号染色体之间的易位，即t(8;21)，会导致产生AML1/MTG8(ETO)融合转录本。AML1基因的产物包含一个进化上保守的128个氨基酸的区域，称为“Runt结构域”，它是在PEBP2位点与DNA结合所必需的。主要包含Runt结构域的AML1蛋白片段以及与融合转录本互补的反义寡核苷酸强烈抑制了源自含有t(8;21)的急性髓系白血病的细胞系的生长并诱导其分化。这些结果表明，通过PEBP2位点的转录调控对于t(8;21)白血病细胞的生长和分化至关重要，并且嵌合基因的产物负责维持白血病表型。
