Cellular origin and pathophysiology of chronic lymphocytic leukemia.
Cellular origin and pathophysiology of chronic lymphocytic leukemia.
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DOI：
10.1084/jem.20120833
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发表时间：
2012-11-19
期刊：
影响因子：
--
通讯作者：
Küppers R
中科院分区：
文献类型：
--
作者：
Seifert M;Sellmann L;Bloehdorn J;Wein F;Stilgenbauer S;Dürig J;Küppers R
未突变CLL来源于未突变的成熟CD5+ B细胞，而突变CLL来源于CD5+CD27+生发后中心B细胞。慢性淋巴细胞白血病（CLL）的细胞起源仍有争议，尽管这一信息对了解其发病机制至关重要。对CLL和来自人血液和脾脏的主要正常B细胞亚群的转录组分析显示，免疫球蛋白可变区（IgV）基因未突变的CLL来自未突变的成熟CD5+ B细胞，而突变的CLL来自一个不同的、以前未被识别的CD5+CD27+生发后中心B细胞亚群。定型V基因重排在CD5+ B细胞中富集，为CD5+ B细胞衍生CLL提供了独立证据。值得注意的是，这些CD5+ B细胞群包括已经在年轻健康成人中发现的低克隆扩增，推测代表了CLL前体病变单克隆B细胞淋巴细胞增多症之前CLL发展的早期阶段。最后，我们确定了不受调控的蛋白，包括EBF1和KLF转录因子，这些蛋白在之前的CLL和常规B细胞比较中未被检测到。
Unmutated CLL derives from unmutated mature CD5+ B cells and mutated CLL derives from CD5+CD27+ post–germinal center B cells. The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information is critical to understanding its pathogenesis. Transcriptome analyses of CLL and the main normal B cell subsets from human blood and spleen revealed that immunoglobulin variable region (IgV) gene unmutated CLL derives from unmutated mature CD5+ B cells and mutated CLL derives from a distinct, previously unrecognized CD5+CD27+ post–germinal center B cell subset. Stereotyped V gene rearrangements are enriched among CD5+ B cells, providing independent evidence for a CD5+ B cell derivation of CLL. Notably, these CD5+ B cell populations include oligoclonal expansions already found in young healthy adults, putatively representing an early phase in CLL development before the CLL precursor lesion monoclonal B cell lymphocytosis. Finally, we identified deregulated proteins, including EBF1 and KLF transcription factors, that were not detected in previous comparisons of CLL and conventional B cells.
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影响因子：
5.4
作者：
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