Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia.
Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia.
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DOI：
10.1182/blood.v83.8.2038.2038
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发表时间：
1994-04
期刊：
影响因子：
20.3
通讯作者：
A. Bedi;B. Zehnbauer;J. Barber;S. Sharkis;Richard J. Jones
中科院分区：
文献类型：
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作者：
A. Bedi;B. Zehnbauer;J. Barber;S. Sharkis;Richard J. Jones
据推测，BCR-ABL表达通过细胞增殖失调影响慢性粒细胞白血病（CML）的克隆扩增。然而，大多数研究发现，CML中细胞增殖的相对速率并未增加。此外，我们发现CML祖细胞显示出对生长因子的正常增殖反应，并且没有表现出比正常祖细胞更大的增殖潜力。恶性肿瘤的生长取决于细胞产生速率和细胞死亡速率之间的不平衡。我们发现，BCR-ABL的表达不适当地通过抑制细胞凋亡（一种基因编程的主动细胞死亡过程）来抑制CML髓系祖细胞和粒细胞的生长因子非依赖性存活;反义寡核苷酸抑制BCR-ABL表达逆转了对细胞凋亡的抑制以及对存活的增强。程序性细胞死亡率降低似乎是BCR-ABL影响CML白血病克隆扩增的主要机制。
BCR-ABL expression is presumed to effect clonal expansion in chronic myeloid leukemia (CML) by deregulation of cell proliferation. However, most studies have found that relative rates of cell proliferation are not increased in CML. Moreover, we found that CML progenitors display a normal proliferative response to growth factors and do not manifest greater proliferative potential than normal progenitors. Growth of malignancies depends on an imbalance between the rate of cell production and the rate of cell death. We found that BCR-ABL expression inappropriately prolongs the growth factor-independent survival of CML myeloid progenitors and granulocytes by inhibiting apoptosis, a genetically programmed process of active cell death; inhibition of BCR-ABL expression by antisense oligonucleotides reversed the suppression of apoptosis as well as the enhancement of survival. The decreased rate of programmed cell death appears to be the primary mechanism by which BCR-ABL effects expansion of the leukemic clone in CML.