Punish the parent not the progeny
Punish the parent not the progeny
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DOI：
10.1182/blood-2004-08-3373
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发表时间：
2005-03-01
期刊：
影响因子：
20.3
通讯作者：
Holyoake, TL
中科院分区：
文献类型：
--
作者：
Elrick, LJ;Jorgensen, HG;Holyoake, TL
慢性粒细胞白血病（CML）是由一种罕见的原始、静止、BCR-ABL（+）细胞群维持的，是恶性肿瘤的一个很好的例子，其中肿瘤起始细胞是疾病根除的关键。慢性粒细胞白血病也是第一个靶向治疗取代传统化疗的恶性肿瘤。在大量表达断裂点簇区域标记（BCR-ABL）并对酪氨酸激酶抑制剂甲磺酸伊马替尼（IM）敏感的增殖祖细胞中，存在一小部分静止白血病细胞，尽管BCR-ABL转录水平较高，但对IM表现出先天不敏感性。这些细胞在IM治疗后仍然存在，即使达到了明显的完全反应，它们可能解释了分子疾病的持续性。虽然可以认为患者可以存活多年，但仍存在低水平的白血病，但在异基因干细胞移植后，有可能在分子水平上实现疾病清除。IM单药治疗耐药性的出现也支持完全根除疾病，我们认为这仍然是CML的最终治疗目标。因此，消除这些原始CML细胞的新方法可能对治疗策略的发展至关重要。
Chronic myeloid leukemia (CML) is sustained by a rare population of primitive, quiescent, BCR-ABL(+) cells and represents an excellent example of a malignancy in which tumor-initiating cells represent the key to disease eradication. CML is also the first malignancy for which targeted therapy has replaced conventional chemotherapy. Within a vast excess of proliferating progenitor cells that express breakpoint cluster regionabelson (BCR-ABL) and are exquisitely sensitive to the tyrosine kinase inhibitor imatinib mesylate (IM) resides a small population of quiescent leukemic cells that, despite higher levels of BCR-ABL transcripts, exhibits innate insensitivity to IM. These cells remain after IM therapy, even when apparently complete responses are achieved, and they probably explain molecular disease persistence. Although it can be argued that patients may survive for many years with low levels of leukemia still present, it is possible to achieve disease clearance at the molecular level following an allogeneic stem cell transplantation. The emergence of drug resistance with IM monotherapy also argues in favor of complete disease eradication that we believe should remain the ultimate therapeutic goal in CML. New approaches to the elimination of these primitive CML cells may thus be crucial to the development of curative strategies.