A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia
A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia
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DOI：
10.1182/blood.v98.4.1166
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发表时间：
2001-08-15
期刊：
影响因子：
20.3
通讯作者：
Goodell, MA
中科院分区：
文献类型：
--
作者：
Wulf, GG;Wang, RY;Goodell, MA
急性髓细胞白血病（AML）的造血干细胞是有争议的。流式细胞术和DNA结合染料Hoechst 33342以前被用来识别一个独特的小鼠造血干细胞亚群，称为侧群（SP），它迅速排出Hoechst染料，并可以重建致死照射小鼠的骨髓。在这里，SP细胞在人类AML中的患病率和致病作用进行了研究。在61例患者中，超过80%的患者骨髓中发现了这种细胞，并且具有主要的CD 34（低/-）免疫表型。重要的是，在所有11例检查的活动性疾病中，他们携带AML的细胞遗传学标记，在5例完全血液学缓解的病例中，有2例携带AML的细胞遗传学标记。柔红霉素和米托蒽醌荧光发射谱的比较显示，白血病SP细胞比非SP细胞具有更高的药物效应。28例SP细胞移植中有3例在非肥胖糖尿病-严重联合免疫缺陷小鼠中产生明显的AML样疾病。低，但持续数量的白血病SP细胞检测到的分子和免疫学分析，其余小鼠的一半。总之，这些发现表明SP细胞经常参与人类AML，并可能是白血病转化的靶点。他们还提出了一种机制，SP细胞可以逃脱细胞生长抑制药物的作用，并可能最终导致白血病复发。
The hematopoietic stem cell underlying acute myeloid leukemia (AML) is controversial. Flow cytometry and the DNA-binding dye Hoechst 33342 were previously used to identify a distinct subset of murine hematopoietic stem cells, termed the side population (SP), which rapidly expels Hoechst dye and can reconstitute the bone marrow of lethally irradiated mice. Here, the prevalence and pathogenic role of SP cells in human AML were investigated. Such cells were found in the bone marrow of more than 80% of 61 patients and had a predominant CD34(low/-) immunophenotype. importantly, they carried cytogenetic markers of AML in all 11 cases of active disease examined and in 2 out of 5 cases in complete hematological remission. Comparison of daunorubicin and mitoxantrone fluorescence emission profiles revealed significantly higher drug eff lux from leukemic SP cells than from non-SP cells. Three of 28 SP cell transplants generated overt AML-like disease in nonobese diabetic-severe combined immunodeficient mice. Low but persistent numbers of leukemic SP cells were detected by molecular and immunological assays in half of the remaining mice. Taken together, these findings indicate that SP cells are frequently involved in human AML and may be a target for leukemic transformation. They also suggest a mechanism by which SP cells could escape the effects of cytostatic drugs and might eventually contribute to leukemia relapse.