CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL
CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL
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CD34 CD38 CD19 以及 CD34 CD38-CD19 细胞是人 B 前体 ALL 中具有自我更新能力的白血病起始细胞
DOI：
10.1038/leu.2008.83
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发表时间：
2008-06-01
期刊：
影响因子：
11.4
通讯作者：
Ishikawa, F.
中科院分区：
文献类型：
--
作者：
Kong, Y.;Yoshida, S.;Ishikawa, F.
最近报道了罕见的恶性干细胞的存在，提供了恶性细胞的层次。在人类急性髓细胞性白血病（AML）中，白血病干细胞（LSC）表型限制在CD 34 + CD 38-部分内。为了了解原发性人B前体急性淋巴细胞白血病（B-ALL）恶性细胞的来源，我们建立了一种新的体内异种移植模型。将来自三名儿科B-ALL患者的纯化的CD 34 + CD 38 + CD 19+、CD 34 + CD 38-CD 19+和CD 34 + CD 38-CD 19-骨髓（BM）或外周血（PB）细胞静脉内注射到亚致死照射的新生NOD/SCID/IL 2 r γ（null）小鼠中。我们发现，CD 34 + CD 38 + CD 19+和CD 34 + CD 38-CD 19+细胞在原发性受者中均引发B-ALL，而CD 34 + CD 38-CD 10-CD 19-细胞的受者显示正常的人类造血重建。移植CD 34 + CD 38 + CD 19+细胞和移植CD 34 + CD 38-CD 19+细胞受者的脾、肝、肾浸润程度相似。在所研究的三个病例中，CD 34 + CD 38 + CD 19+细胞的移植导致了第二受者中B-ALL的发展，证明了自我更新能力。CD 34 + CD 38 + CD 19+自我更新B-ALL细胞的鉴定提出了一个不同于AML的白血病起始细胞（LIC）的层次结构。在NOD/SCID/IL 2 r γ（null）受体中患者B-ALL的再发生为直接研究白血病发生和开发治疗策略提供了强有力的工具。
The presence of rare malignant stem cells supplying a hierarchy of malignant cells has recently been reported. In human acute myelogenous leukemia (AML), the leukemia stem cells (LSCs) have been phenotypically restricted within the CD34+CD38- fraction. To understand the origin of malignant cells in primary human B-precursor acute lymphocytic leukemia (B-ALL), we established a novel in vivo xenotransplantation model. Purified CD34+CD38+CD19+, CD34+CD38-CD19+ and CD34+CD38-CD19- bone marrow ( BM) or peripheral blood (PB) cells from three pediatric B-ALL patients were intravenously injected into sublethally irradiated newborn NOD/SCID/IL2r gamma(null) mice. We found that both CD34+CD38+CD19+ and CD34+CD38-CD19+ cells initiate B-ALL in primary recipients, whereas the recipients of CD34+CD38-CD10-CD19- cells showed normal human hematopoietic repopulation. The extent of leukemic infiltration into the spleen, liver and kidney was similar between the recipients transplanted with CD34+CD38+CD19+ cells and those transplanted with CD34+CD38-CD19+ cells. In each of the three cases studied, transplantation of CD34+CD38+CD19+ cells resulted in the development of B-ALL in secondary recipients, demonstrating self-renewal capacity. The identification of CD34+CD38+ CD19+ self-renewing B-ALL cells proposes a hierarchy of leukemia-initiating cells (LICs) distinct from that of AML. Recapitulation of patient B-ALL in NOD/SCID/IL2r gamma(null) recipients provides a powerful tool for directly studying leukemogenesis and for developing therapeutic strategies.