Heterogeneous somatic hypermutation status confounds the cell of origin in hairy cell leukemia

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• 作者：Thorsé ; lius ; Mia ; Walsh ; Sarah H. ; Thunberg ; Ulf ; Hagberg ; Hans ; Sundstr&ouml ; m ; Christer ; et. al.
• 关键词：Hairy cell leukemia ; Immunoglobulin genes ; V_H genes ; Somatic hypermutation status ; Intraclonal heterogeneity
• 刊名：Leukemia Research
• 出版年：2005
• 出版时间：February, 2005
• 年：2005
• 卷：29
• 期：2
• 页码：153-158
• 全文大小：123 K

文摘

Hairy cell leukemia (HCL) is thought to arise from a post-germinal center (GC) B-cell, however the exact normal counterpart remains unclear. We performed V_H gene analysis of 32 HCL cases, revealing somatically mutated V_H genes (<98 % homology) in 27 cases and unmutated V_H genes in five cases, four of which displayed germline V_H genes. Intraclonal heterogeneity was evident in the majority of eight mutated HCLs investigated, although at a lower level compared to GC-derived lymphomas. A novel finding of preferential V_H3-30 gene usage was detected (19 % of HCLs). Our data confounds the postulated post-GC origin in HCL considering (1) the finding of unmutated HCLs, generally correlating with a pre-GC origin, and (2) the presence of intraclonal variation in mutated HCLs. The latter suggests that the transformed B-cell was frozen when it still had an active mutation process, implying a closer relation to the GC than previously assumed. Furthermore, restricted V_H3-30 usage indicates that antigen selection could be a promoting factor in HCL development.