Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Leuk Res. 2011 Aug;35(8):1074-9. doi: 10.1016/j.leukres.2010.11.012. Epub 2010 Dec 15.
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.
bcr/abl 融合基因是慢性髓系白血病（CML）的标记基因，成为 CML 治疗的靶点。虽然伊马替尼为 CML 治疗开辟了新途径，但 bcr/abl 融合蛋白突变导致的耐药性刺激了寻找新的分子来抑制 bcr/abl 表达的研究。在我们的研究中，发现一种新型 2-氨基甾体（H89465）在治疗 CML 方面具有特殊机制。H89465 抑制非耐药和耐药 CML 细胞（如 K562、Meg-01 和临床原发性 CML 细胞）的增殖。它延长了接种 K562 白血病细胞的 NOD/SCID 小鼠的存活时间。其作用机制与下调 bcr/abl mRNA 表达有关，随后降低 CML 细胞中的 BCR/ABL 蛋白表达和酪氨酸激酶活性。我们的结果表明，H89465 具有治疗人类 CML 的潜力。
