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.
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.
Sakakura
C
C
Department of Viral Oncology, Kyoto University, Japan.
Yamaguchi-Iwai
Y
Y
Satake
M
M
Bae
S C
SC
Takahashi
A
A
Ogawa
E
E
Hagiwara
A
A
Takahashi
T
T
Murakami
A
A
Makino
K
K
D000208:Acute Disease; D001483:Base Sequence; D001667:Binding, Competitive; D002454:Cell Differentiation; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D004268:DNA-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D006131:Growth Inhibitors; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000502:physiology*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D011993:Recombinant Fusion Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors