Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia
Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia
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DOI：
10.1016/j.ccr.2011.06.029
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发表时间：
2011-08-16
期刊：
影响因子：
50.3
通讯作者：
Akashi, Koichi
中科院分区：
文献类型：
--
作者：
Kikushige, Yoshikane;Ishikawa, Fumihiko;Akashi, Koichi
我们在此报告，在慢性淋巴细胞白血病 (CLL) 中，在造血干细胞 (HSC) 阶段就已经获得了产生克隆 B 细胞的倾向。从 CLL 患者中纯化的 HSC 表现出淋巴谱系基因启动，并产生大量多克隆 B 细胞祖细胞。引人注目的是，它们在异种受体中成熟为 B 细胞始终局限于具有 CLL 样表型的单克隆或寡克隆。这些 B 细胞克隆独立于原始的 CLL 克隆，因为它们有自己的免疫球蛋白 VDJ 基因。此外，他们优先使用人类 CLL 中常用的 VH 基因，这可能反映了 B 细胞受体信号传导在克隆选择中的作用。这些数据表明，即使在成熟的淋巴肿瘤中，HSC 也可以参与白血病的发生。
We report here that in chronic lynnphocytic leukemia (CLL), the propensity to generate clonal B cells has been acquired already at the hematopoietic stem cell (HSC) stage. HSCs purified from patients with CLL displayed lymphoid-lineage gene priming and produced a high number of polyclonal B cell progenitors. Strikingly, their maturation into B cells was restricted always to mono- or oligo-clones with CLL-like phenotype in xenogeneic recipients. These B cell clones were independent of the original CLL clones because they had their own immunoglobulin VDJ genes. Furthermore, they used preferentially VH genes frequently used in human CLL, presumably reflecting the role of B cell receptor signaling in clonal selection. These data suggest that HSCs can be involved in leukemogenesis even in mature lymphoid tumors.