Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides.
Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides.
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DOI：
10.1126/science.1857987
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发表时间：
1991-08
期刊：
影响因子：
56.9
通讯作者：
C. Szczylik;T. Skorski;N. Nicolaides;L. Manzella;L. Malaguarnera;D. Venturelli;A. Gewirtz;B. Calabretta
中科院分区：
文献类型：
--
作者：
C. Szczylik;T. Skorski;N. Nicolaides;L. Manzella;L. Malaguarnera;D. Venturelli;A. Gewirtz;B. Calabretta
为了确定BCR-ABL基因在慢性粒细胞白血病患者的母细胞增殖中的作用，将白血病母细胞暴露于与两个鉴定的BCR-ABL连接互补的合成18聚体寡脱氧核苷酸。白血病集落形成受到抑制，而正常骨髓祖细胞的粒细胞-巨噬细胞集落形成不受影响。当将等比例的正常骨髓祖细胞和原始细胞混合，暴露于寡脱氧核苷酸，并测定残留集落形成时，大多数残留细胞是正常的。这些研究结果表明，在维持白血病表型和基因靶向选择性杀死肿瘤细胞的可行性的功能性BCR-ABL基因的要求。
To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte-macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells were mixed, exposed to the oligodeoxynucleotides, and assayed for residual colony formation, the majority of residual cells were normal. These findings demonstrate the requirement for a functional BCR-ABL gene in maintaining the leukemic phenotype and the feasibility of gene-targeted selective killing of neoplastic cells.