Re-evaluating the role of BCR/ABL in chronic myelogenous leukemia.
Re-evaluating the role of BCR/ABL in chronic myelogenous leukemia.
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重新评估BCR/ABL在慢性骨髓性白血病中的作用。
DOI：
10.4161/23723548.2014.963450
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发表时间：
2014-07
影响因子：
2.1
通讯作者：
Mgbemena VE
中科院分区：
文献类型：
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作者：
Ross TS;Mgbemena VE
慢性粒细胞白血病（CML）需要BCR/ABL酪氨酸激酶的疾病发作和维持。因此，CML可以用酪氨酸激酶抑制剂（TKI）如伊马替尼成功治疗。大多数患者通过每日TKI治疗维持疾病抑制状态数年，在许多情况下，这种治疗可防止进展至急变期。如果停用TKI，95%的患者由于持续存在白血病起始细胞（LIC）而再次发生CML。有几种假设描述了导致CML中LIC持续存在的潜在机制，但支持证据有限。此外，在停止TKI治疗并“治愈”（即，在无治疗缓解期），大多数在其造血组织中具有残留的BCR/ABL表达细胞。也有没有CML诊断的健康个体在其造血细胞的一部分中表达BCR/ABL突变。最后，从Bcr基因座表达BCR/ABL作为敲入突变的小鼠不会发生CML。这些小鼠的BCR/ABL水平低于发生CML的逆转录病毒或BCR/ABL转基因模型。了解为什么从Bcr基因座表达BCR/ABL的小鼠和一些表达BCR/ABL的人不患有CML，将为预防或治愈这种疾病的治疗提供见解。
Chronic myelogenous leukemia (CML) requires the BCR/ABL tyrosine kinase for disease onset and maintenance. As a result, CML can be successfully treated with tyrosine kinase inhibitors (TKIs) such as imatinib. Most patients are maintained in a disease-suppressed state on daily TKI therapy for several years and in many cases this treatment prevents progression to the blast phase. If the TKI is discontinued, CML redevelops in 95% of patients as a result of persisting leukemia initiating cells (LICs). There are several hypotheses that describe the potential mechanism(s) responsible for LIC persistence in CML, but supporting evidence is limited. Furthermore, of the few patients who discontinue TKI therapy and are “cured” (i.e., in treatment-free remission), most have residual BCR/ABL-expressing cells in their hematopoietic tissues. There are also healthy individuals without a CML diagnosis who express the BCR/ABL mutation in a fraction of their hematopoietic cells. Finally, mice that express BCR/ABL from the Bcr locus as a knockin mutation do not develop CML. These mice have lower BCR/ABL levels than retroviral or transgenic models of BCR/ABL that do develop CML. Understanding why mice with BCR/ABL expressed from the Bcr locus and some people that express BCR/ABL are not afflicted with CML will provide insights into therapies to prevent or cure this disease.