Heterogeneous somatic hypermutation status confounds the cell of origin in hairy cell leukemia.
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 VH gene analysis of 32 HCL cases, revealing somatically mutated VH genes (<98% homology) in 27 cases and unmutated VH genes in five cases, four of which displayed germline VH 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 VH3-30 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 VH3-30 usage indicates that antigen selection could be a promoting factor in HCL development.
Thorsélius
Mia
M
Department of Genetics and Pathology, Rudbeck Laboratary, Uppsala University, SE-751 85 Uppsala, Sweden.
Walsh
Sarah H
SH
Thunberg
Ulf
U
Hagberg
Hans
H
Sundström
Christer
C
Rosenquist
Richard
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics*; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007943:Leukemia, Hairy Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*
D007143:Immunoglobulin Heavy Chains