The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells
The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells
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DOI：
10.1038/sj.leu.2401903
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发表时间：
2000-10-01
期刊：
影响因子：
11.4
通讯作者：
Phillips, GL
中科院分区：
文献类型：
--
作者：
Jordan, CT;Upchurch, D;Phillips, GL
最近的研究表明，人类急性髓性白血病 (AML) 中发现的恶性细胞群源自罕见的白血病干细胞 (LSC) 群。几乎所有 AML 亚型均记录有 LSC，表型被描述为 CD34(+)/CD38(-) 或 CD34(+)/HLADR(-)。鉴于这些原始细胞在白血病疾病持续存在中的潜在关键作用，我们试图进一步研究它们的分子和细胞特征。使用原发性 AML 组织进行的流式细胞术研究表明，18 个原发标本中有 16 个的 CD34(+)/CD38(-) 细胞（98+/-2% 阳性）中强烈表达白介素 3 受体 α 链（IL-3R α 或 CD123）。相反，正常骨髓来源的CD34(+)/CD38(-)细胞实际上没有检测到CD123抗原的表达。为了评估IL-3Ra阳性细胞的功能作用，将纯化的CD34(+)/CD123(+)白血病细胞移植到免疫缺陷的NOD/SCID小鼠中。这些实验表明CD123(+)细胞能够在体内建立和维持白血病群体。为了开始阐明 CD123 在白血病中的生物学作用，我们对原发性 AML 样本的 MAPK、Akt 和 Stat5 通路中的信号转导活性进行了分析。没有检测到对 IL-3 刺激的磷酸化反应，因此表明 CD123 在传统的 IL-3 介导的信号传导中不活跃。总的来说，这些数据表明 CD123 代表原始白血病干细胞的独特标记。鉴于该受体在 LSC 上的强烈表达，我们认为靶向 CD123 可能是优先消融 AML 细胞的一种有前途的策略。
Recent studies suggest that the population of malignant cells found in human acute myelogenous leukemia (AML) arises from a rare population of leukemic stem cells (LSCs). LSCs have been documented for nearly all AML subtypes and have been phenotypically described as CD34(+)/CD38(-) or CD34(+)/HLADR(-). Given the potentially critical role of these primitive cells in perpetuating leukemic disease, we sought to further investigate their molecular and cellular characteristics. Flow cytometric studies using primary AML tissue showed that the interleukin-3 receptor alpha chain (IL-3R alpha or CD123) was strongly expressed in CD34(+)/CD38(-) cells (98+/-2% positive) from 16 of 18 primary specimens. Conversely, normal bone marrow derived CD34(+)/CD38(-) cells showed virtually no detectable expression of the CD123 antigen. To assess the functional role of IL-3Ra positive cells, purified CD34(+)/CD123(+) leukemia cells were transplanted into immune deficient NOD/SCID mice. These experiments showed that CD123(+) cells were competent to establish and maintain leukemic populations in vivo. To begin to elucidate a biological role for CD123 in leukemia, primary AML samples were analyzed with respect to signal transduction activity in the MAPK, Akt, and Stat5 pathways. Phosphorylation was not detected in response to IL-3 stimulation, thereby suggesting CD123 is not active in conventional IL-3-mediated signaling. Collectively, these data indicate that CD123 represents a unique marker for primitive leukemic stem cells. Given the strong expression of this receptor on LSCs, we propose that targeting of CD123 may be a promising strategy for the preferential ablation of AML cells.