Moores UCSD Cancer Center, University of California, 3855 Health Sciences Drive, Mail Code 0820, La Jolla, CA 92093-0820, USA.
Int J Hematol. 2010 Jun;91(5):748-52. doi: 10.1007/s12185-010-0615-8. Epub 2010 Jun 10.
Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), but it does not cure the disease. Many patients never achieve significant cytogenetic or molecular responses. Some develop resistance to the drug, while others are simply unable to tolerate it. Unfortunately, most will relapse if the drug is discontinued. This is particularly true in patients with advanced disease, who tend to develop resistance rapidly and are unlikely to achieve durable remission with single-agent tyrosine kinase inhibitor therapy. A growing body of evidence suggests that the reason imatinib does not cure CML is that it is unable to eradicate the leukemic stem cells (LSC). LSC are a tiny population of cancer cells with the capacity to recapitulate the disease. These quiescent cells have subverted properties of normal hematopoietic stem cells, allowing them to avoid apoptosis, evade innate immunity, renew themselves, and survive long term. Here, we review the studies that have identified the deregulated molecular pathways responsible for the generation of CML stem cells and discuss implications for therapy.
伊马替尼已经彻底改变了慢性髓性白血病（CML）的治疗方法，但它并不能治愈这种疾病。许多患者从未达到显著的细胞遗传学或分子反应。一些患者对药物产生耐药性，而另一些患者则根本无法耐受。不幸的是，如果停止用药，大多数患者都会复发。对于晚期疾病患者来说尤其如此，他们往往会迅速产生耐药性，并且单药酪氨酸激酶抑制剂治疗不太可能实现持久缓解。越来越多的证据表明，伊马替尼不能治愈 CML 的原因是它无法根除白血病干细胞（LSC）。LSC 是一小群具有重现疾病能力的癌细胞。这些静止的细胞颠覆了正常造血干细胞的特性，使它们能够避免细胞凋亡、逃避先天免疫、自我更新并长期存活。在这里，我们回顾了确定导致 CML 干细胞产生的失调分子途径的研究，并讨论了其对治疗的影响。
