Mutations of the AML1 gene in myelodysplastic syndrome and their functional implications in leukemogenesis

被引:145
作者
Imai, Y
Kurokawa, M
Izutsu, K
Hangaishi, A
Takeuchi, K
Maki, K
Ogawa, S
Chiba, S
Mitani, K
Hirai, H
机构
[1] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan
[2] Univ Tokyo, Grad Sch Med, Dept Pathol, Bunkyo Ku, Tokyo 1138655, Japan
关键词
D O I
10.1182/blood.V96.9.3154.h8003154_3154_3160
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The AML1 gene encodes a DNA-binding protein that contains the runt domain and is the most frequent target of translocations associated with human leukemias. Here, point mutations of the AML1 gene, V105ter (single-letter amino acid code) and R139G, (single-letter amino acid codes) were identified in 2 cases of myelodysplastic syndrome (MDS) by means of the reverse transcriptase-polymerase chain reaction single-strand conformation polymorphism method. Both mutations are present in the region encoding the runt domain of AML1 and cause loss of the DNA-binding ability of the resultant products. Of these mutants, V105ter has also lost the ability to heterodimerize with polyomavirus enhancer binding protein 2/core binding factor beta (PEBP2 beta /CBF beta). On the other hand, the R139G mutant acts as a dominant negative inhibitor by competing with wild-type AML1 for interaction with PEBP2 beta /CBF beta. This study is the first report that describes mutations of AML1 in patients with MDS and the mechanism whereby the mutant acts as a dominant negative inhibitor of wild-type AML1. (C) 2000 by The American Society of Hematology.
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收藏
页码:3154 / 3160
页数:7
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