Acute myeloid leukemia stem cells and CD33-targeted immunotherapy
Acute myeloid leukemia stem cells and CD33-targeted immunotherapy
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DOI：
10.1182/blood-2011-11-325050
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发表时间：
2012-06-28
期刊：
影响因子：
20.3
通讯作者：
Bernstein, Irwin D.
中科院分区：
文献类型：
--
作者：
Walter, Roland B.;Appelbaum, Frederick R.;Bernstein, Irwin D.
虽然癌症干细胞作为治疗靶点的鉴定现在在许多人类恶性肿瘤中被积极追求，但急性髓性白血病（AML）中的白血病干细胞是这种策略的范例。克隆分析表明这些细胞的异源性，表明存在由转化的多能CD 33（-）干细胞引起的白血病以及由定向CD 33（+）髓样前体细胞引起或主要涉及定向CD 33（+）髓样前体细胞的白血病。后者白血病，这可能与一个内在的更好的预后，提供了一个特别有吸引力的干细胞定向治疗的目标。用吉妥珠单抗靶向⑶ 33分化抗原是这种方法的第一次尝试。新出现的临床数据表明，吉妥珠单抗不仅对急性早幼粒细胞白血病有效，而且与常规化疗联合使用，对其他有利和中等风险AML也有效，为该策略的有效性提供了第一个原则性证据。在此，我们回顾了AML中干细胞性质的研究，讨论了CD 33导向治疗有效性的临床数据，并考虑了各种AML亚群成功和失败的机制基础。（血。2012; 119（26）：6198-6208）
Although the identification of cancer stem cells as therapeutic targets is now actively being pursued in many human malignancies, the leukemic stem cells in acute myeloid leukemia (AML) are a paradigm of such a strategy. Heterogeneity of these cells was suggested by clonal analyses indicating the existence of both leukemias resulting from transformed multi-potent CD33(-) stem cells as well others arising from, or predominantly involving, committed CD33(+) myeloid precursors. The latter leukemias, which may be associated with an intrinsically better prognosis, offer a particularly attractive target for stem cell-directed therapies. Targeting the CD33 differentiation antigen with gemtuzumab ozogamicin was the first attempt of such an approach. Emerging clinical data indicate that gemtuzumab ozogamicin is efficacious not only for acute promyelocytic leukemia but, in combination with conventional chemotherapy, also for other favorable- and intermediate-risk AMLs, providing the first proof-of-principle evidence for the validity of this strategy. Herein, we review studies on the nature of stem cells in AML, discuss clinical data on the effectiveness of CD33-directed therapy, and consider the mechanistic basis for success and failure in various AML subsets. (Blood. 2012; 119(26):6198-6208)