The introduction of Abl tyrosine kinase inhibitors (TKI; that is, imatinib, dasatinib and nilotinib) as front-line therapy completely changed the course of chronic myelogenous leukemia (CML) to the point that most of the TKI-responsive newly diagnosed CML patients can be considered ‘clinically’ cured and their progression into blast crisis (BC) a rare event. However, a therapy for those patients who transform is still lacking, and TKIs do not eradicate CML at the stem cell level, therefore leaving a reservoir of cancer stem cells in a dormant stage. Thus, it is not surprising that the focus of CML research has shifted significantly toward the dissection of the mechanisms regulating the survival and self-renewal of TKI-resistant Philadelphia-positive leukemic chronic phase and BC stem cells, with the ultimate goal of developing small molecules capable of selectively killing leukemic but not normal hematopoietic stem cells, thereby achieving a ‘biological’ cure for this disease.

Abl 酪氨酸激酶抑制剂（TKI；即伊马替尼、达沙替尼和尼罗替尼）作为一线治疗的引入彻底改变了慢性粒细胞性白血病（CML）的病程，以至于大多数对 TKI 有反应的新诊断 CML 患者可以被认为是“临床上”治愈的，他们进展为爆炸危机 (BC) 是一种罕见的事件。然而，仍然缺乏针对那些发生转化的患者的治疗方法，并且 TKI 不能在干细胞水平上根除 CML，因此使癌症干细胞库处于休眠阶段。因此，CML 研究的重点已显着转向剖析调节 TKI 耐药费城阳性白血病慢性期和 BC 干细胞的存活和自我更新的机制，这并不奇怪，