A small molecule significantly inhibits the bcr/abl fusion gene at the mRNA level in human chronic myelogenous leukemia

被引：4

作者：

He, Qun ^{[1
]}

Dong, Jun ^{[1
]}

Zhen, Huanying ^{[1
]}

Ying, Yalin ^{[1
]}

Zhang, Jun ^{[1
]}

Li, Qiong ^{[1
]}

Li, Birong ^{[1
]}

Zhou, Yang ^{[1
]}

机构：

[1] Cent S Univ, Dept Physiol, Xiangya Sch Med, Changsha 410078, Hunan, Peoples R China

来源：

LEUKEMIA RESEARCH | 2011年 / 35卷 / 08期

关键词：

H89465; 2-Aminosteroid; K562; Meg-01; bcr/abl; T315I; CML; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; PHILADELPHIA-CHROMOSOME; CLINICAL RESISTANCE; CELL-LINE; DIFFERENTIATION; MECHANISMS; INDUCTION; IMATINIB; HL-60;

D O I：

10.1016/j.leukres.2010.11.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Bcr/abl fusion gene is the marker gene in chronic myelogenous leukemia (CML) and becomes the target for CML therapy. Although Imatinib opened a new way to treat CML, the resistance to the drug caused by bcr/abl fusion protein mutation stimulated search for new molecules to inhibit bcr/abl expression. In our research, it was found that a novel 2-aminosteroid (H89465) possessed special mechanism in treating CML. H89465 inhibits the proliferation of both non-resistant and resistant CML cells such as K562, Meg-01 and clinical primary CML cells. It prolongs the survival time of NOD/SCID mice inoculated with K562 leukemia cells. The mechanism underlying the effects is concerned with down-regulation of bcr/abl mRNA expression followed by decreasing the BCR/ABL protein expression and tyrosine kinase activity in CML cells. Our results demonstrate that H89465 possesses the therapeutic potential in treating human CML. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1074 / 1079

页数：6

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