A C-MYB ANTISENSE OLIGODEOXYNUCLEOTIDE INHIBITS NORMAL HUMAN HEMATOPOIESIS INVITRO

A C-MYB ANTISENSE OLIGODEOXYNUCLEOTIDE INHIBITS NORMAL HUMAN HEMATOPOIESIS INVITRO
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DOI:
10.1126/science.2461588
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发表时间:
1988-12-02
期刊:
影响因子:
56.9
通讯作者:
CALABRETTA, B
CALABRETTA, B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
GEWIRTZ, AM;CALABRETTA, B

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由原癌基因c-myb编码的核蛋白被认为在造血过程中起重要作用,但这一功能的直接证据一直缺乏。为了解决这个组织,正常人骨髓单个核细胞暴露于c-myb正义和反义合成寡脱氧核苷酸,造血集落形成和成熟的影响进行了检查。这些细胞暴露于c-myb反义寡脱氧核苷酸导致集落大小和数量减少,对残留集落细胞的成熟没有明显影响。暴露于c-myb正义或不相关的反义寡核苷酸则没有这种作用。这些结果表明:(i)c-myb在调节正常人造血中起关键作用;(ii)反义寡核苷酸和造血细胞培养技术的联合使用将为研究原癌基因或其他特定基因编码的蛋白质在正常人造血中的作用提供有力的工具。
The nuclear protein encoded by the proto-oncogene c-myb has been hypothesized to play an important role in the process of hematopoiesis, but direct proof of this function has been lacking. To address this tissue, normal human bone marrow mononuclear cells were exposed to c-myb sense and antisense synthetic oligodeoxynucleotides, and the effects on hematopoietic colony formation and maturation were examined. Exposure of these cells to c-myb antisense, oligodeoxynucleotides resulted in a decrease in both colony size and number, without apparent effect on the maturation of residual colony cells. Exposure to c-myb sense, or irrelevant antisense, oligonucleotides had no such effect. These results show that (i) c-myb plays a critical role in regulating normal human hematopoiesis and (ii) the combined use of antisense oligodeoxynucleotides and hematopoietic cell culture techniques will provide a powerful tool for studying the role of proteins encoded by proto-oncogenes, or other specific genes, in normal human hematopoiesis.