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首页> 外文期刊>Leukemia Research and Treatment >The Interface between BCR-ABL-Dependent and -Independent Resistance Signaling Pathways in Chronic Myeloid Leukemia
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The Interface between BCR-ABL-Dependent and -Independent Resistance Signaling Pathways in Chronic Myeloid Leukemia

机译:慢性粒细胞白血病中BCR-ABL依赖性和非依赖性耐药信号通路之间的接口

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Chronic myeloid leukemia (CML) is a clonal hematopoietic disorder characterized by the presence of the Philadelphia chromosome which resulted from the reciprocal translocation between chromosomes 9 and 22. The pathogenesis of CML involves the constitutive activation of the BCR-ABL tyrosine kinase, which governs malignant disease by activating multiple signal transduction pathways. The BCR-ABL kinase inhibitor, imatinib, is the front-line treatment for CML, but the emergence of imatinib resistance and other tyrosine kinase inhibitors (TKIs) has called attention for additional resistance mechanisms and has led to the search for alternative drug treatments. In this paper, we discuss our current understanding of mechanisms, related or unrelated to BCR-ABL, which have been shown to account for chemoresistance and treatment failure. We focus on the potential role of the influx and efflux transporters, the inhibitor of apoptosis proteins, and transcription factor-mediated signals as feasible molecular targets to overcome the development of TKIs resistance in CML.
机译:慢性粒细胞白血病(CML)是一种克隆性造血疾病,其特征是费城染色体的存在,这是由染色体9和22之间的相互易位引起的。CML的发病机制涉及控制恶性的BCR-ABL酪氨酸激酶的组成性激活。通过激活多种信号转导途径来治疗这种疾病。 BCR-ABL激酶抑制剂伊马替尼是CML的一线治疗方法,但是伊马替尼耐药性和其他酪氨酸激酶抑制剂(TKIs)的出现引起了人们对其他耐药机制的关注,并导致人们寻求替代药物治疗。在本文中,我们讨论了我们目前对与BCR-ABL相关或不相关的机制的理解,这些机制已被证明可以解释化学耐药性和治疗失败。我们专注于潮气和外流转运蛋白,凋亡蛋白的抑制剂和转录因子介导的信号作为克服CML中TKIs耐药性发展的可行分子靶标的潜在作用。

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