Identification of two transcripts of AML1/ETO-fused gene in t(8;21) leukemic cells and expression of wild-type ETO gene in hematopoietic cells.
The t(8;21) is a common chromosomal abnormality, preferentially associated with acute leukemia showing features of myeloid differentiation. Recently, two genes--AML1, which has a unique runt domain, and ETO (MTG8)--have been isolated from the chromosomal breakpoint. In this study, we isolated and identified two fused transcripts from a leukemic cell line carrying t(8;21). AML1 and ETO were fused at the same position in these transcripts. One of the transcripts codes a unique domain, including two zinc finger domains and three proline- and one leucine-rich region. The other transcript codes only for one proline- and leucine-rich region but lacks zinc finger domains. We demonstrated by polymerase chain reaction (PCR) analysis that 1) these two transcripts are consistently expressed in leukemic cells with t(8;21) obtained from patients and 2) expression of AML1 was not restricted to the particular stage of hematopoietic differentiation but was present in all hematopoietic cells investigated. We also provide evidence that two wild types of ETO transcripts containing the region of the ETO gene in fused transcripts are expressed in hematopoietic cells from different lineages. The widespread expression of AML1 and ETO in hematopoietic cells suggests a fundamental role of these proteins in hematopoiesis. Furthermore, the differences in the carboxy termini of ETO may modulate the activity of fused proteins resulting from the chromosomal translocation t(8;21).
Era
T
T
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Asou
N
N
Kunisada
T
T
Yamasaki
H
H
Asou
H
H
Kamada
N
N
Nishikawa
S
S
Yamaguchi
K
K
Takatsuki
K
K
D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002478:Cells, Cultured; D002678:Chimera; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D016335:Zinc Fingers
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors