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首页> 外文会议>International Symposium on Amyloidosis >ANALYSIS OF B CELL CLONAL EVOLUTION IN BM AND PBL OF AL AND MM PATIENTS USING GRAPHICAL QUANTIFICATION OF LINEAGE TREES
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ANALYSIS OF B CELL CLONAL EVOLUTION IN BM AND PBL OF AL AND MM PATIENTS USING GRAPHICAL QUANTIFICATION OF LINEAGE TREES

机译：基于血管树木量化的Al和MM患者BM和MM患者的B细胞克隆演化分析

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The objective of this study was to examine the clonal relationships between B cells in the periphery and the clonal plasma cells in the bone marrow (BM) in AL, Myeloma (MM) and MM with AL (MM + AL) patients, which use the same light chain germline V gene (VL). The clonal light chain variable (V) gene was identified by PCR, cloning and nucleotide sequencing. Ourdata show that 1/3rd to 1/2 of the peripheral B cell VL gene repertoire is dominated by the clonal light chain gene in AL patients. This dominance is significantly more pronounced in MM patients (with 85-90% of the B cells using the same germline VL gene as the clonal plasma cell in the BM). The clonal relationship between the PBL and BM populations was further confirmed by Ig VH gene analysis. We used a rigorous computer-aided algorithm for extracting the information contained in the lineage trees, using the terms of mathematical graph theory. Lineage tree analysis has allowed us to obtain a high-resolution analysis of nucleotide sequences from these patients in order to determine the process of clonal selection and evolution in AL and MM. This analysis demonstrates the presence of intra-clonal variations within the BM clones, suggesting that these B cells may be seeded into the BM in "waves". In most patients, the data indicate that the BM clones are derived from the PBL clones, confirming that the clonogenic B cells in the periphery represent a precursor population. The mathematical analysis also reveals that there are significantly more mutations in the VL genes of AL and MM patients compared to normals suggesting either a faster rate of mutation or greater duration of exposure to the mutationa! process. Additionally, the AL BM sequences show more mutations than the PBL sequences, seeming to suggest lower antigenic selection pressure in the shaping of these trees. In conclusion, lineage tree analysis and the novel mathematical approach of quantifying tree properties provides significant insight into the mechanisms of clonal evolution in the pathogenesis of AL and related plasma cell disorders.
机译：本研究的目的是检查B细胞之间在周边和克隆浆细胞克隆关系在AL，骨髓瘤（MM）和MM骨髓（BM）与AL（MM + AL）患者，其中使用相同的轻链条种系V基因（VL）。通过PCR，克隆和核苷酸测序鉴定克隆光链可变（V）基因。 Ourdata显示，外周B细胞VL基因曲目中的1/3至1/2位由Al患者中的克隆轻链基因主导。在MM患者中，这种优势在MM患者中明显更明显（使用与BM中的克隆血浆细胞相同的种系VL基因为85-90％的B细胞）。通过Ig VH基因分析进一步证实了PBL和BM群之间的克隆关系。我们使用了一种严格的计算机辅助算法，用于利用数学图论理论的条款提取谱系树中包含的信息。谱系树分析使我们能够从这些患者获得核苷酸序列的高分辨率分析，以确定Al和Mm中的克隆选择和进化的过程。该分析显示BM克隆内克隆内变化的存在，表明这些B细胞可以将这些B细胞接种到“波浪”中的BM中。在大多数患者中，数据表明BM克隆源自PBL克隆，证实周边中的克隆因B细胞代表前体群。数学分析还揭示了Al和MM患者的VL基因中的突变显着与正常突变率更快或更高的暴露于变异的持续时间！过程。另外，Al BM序列显示出比PBL序列更多的突变，似乎在这些树的成形中表明较低的抗原选择压力。总之，谱系树分析和量化树质的新颖数学方法提供了对Al和相关血浆细胞紊乱的发病机制的克隆演化机制的显着洞察。

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