Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen 45122, Germany.
J Exp Med. 2012 Nov 19;209(12):2183-98. doi: 10.1084/jem.20120833. Epub 2012 Oct 22.
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.
慢性淋巴细胞白血病（CLL）的细胞起源仍存在争议，尽管这些信息对于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表明，未突变的免疫球蛋白可变区（IgV）基因 CLL 来源于未突变的成熟 CD5+ B 细胞，而突变的 CLL 来源于一个先前未被识别的、独特的 CD5+CD27+生发中心后 B 细胞亚群。CD5+B 细胞中富含定型的 V 基因重排，为 CLL 的 CD5+B 细胞起源提供了独立的证据。值得注意的是，这些 CD5+B 细胞群体包括已经在年轻健康成年人中发现的寡克隆扩增，推测代表了 CLL 前体病变单克隆 B 细胞淋巴细胞增多之前的早期阶段。最后，我们鉴定到了失调蛋白，包括 EBF1 和 KLF 转录因子，这些蛋白在之前 CLL 与常规 B 细胞的比较中未被检测到。
