Ahmed Wesam, Van Etten Richard A
1Division of Hematology/Oncology and Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA; and.
Hematology Am Soc Hematol Educ Program. 2013;2013:189-200. doi: 10.1182/asheducation-2013.1.189.
In patients with chronic myeloid leukemia (CML) in chronic phase who have achieved complete molecular remission on imatinib therapy, clinical trials from France and Australia have demonstrated that the majority experience prompt molecular relapse of their leukemia upon discontinuation of the drug, showing that long-term monotherapy with tyrosine kinase inhibitors is not curative in the majority of patients with CML. This has focused attention on strategies to eradicate residual disease in CML that is presumed to arise from malignant Ph+ stem cells, which should result in permanent cure and long-term leukemia-free survival. Here, we review the evidence that targeting CML stem cells will be of clinical benefit and discuss pharmacological and immunological approaches to accomplish this goal. Where possible, we link preclinical studies of CML stem cell biology to emerging results from clinical trials of agents that may target these cells.
在接受伊马替尼治疗已达到完全分子缓解的慢性期慢性髓性白血病（CML）患者中，法国和澳大利亚的临床试验表明，大多数患者在停药后白血病会迅速出现分子复发，这表明酪氨酸激酶抑制剂长期单药治疗并不能治愈大多数CML患者。这使得人们将注意力集中在根除CML残留疾病的策略上，这种残留疾病被认为源自恶性Ph+干细胞，而根除这些干细胞应能实现永久治愈和长期无白血病生存。在此，我们回顾了靶向CML干细胞将具有临床益处的证据，并讨论实现这一目标的药理学和免疫学方法。在可能的情况下，我们将CML干细胞生物学的临床前研究与可能靶向这些细胞的药物的临床试验新结果联系起来。
