Heterogeneous somatic hypermutation status confounds the cell of origin in hairy cell leukemia
2005 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 29, no 2, 153-158 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 29, no 2, 153-158 p.
Adult, Aged, Aged; 80 and over, Base Sequence, Female, Gene Rearrangement; B-Lymphocyte; Heavy Chain, Humans, Immunoglobulin Heavy Chains/analysis/*genetics, Leukemia; B-Cell/genetics/immunology/pathology, Leukemia; Hairy Cell/*genetics/immunology/pathology, Male, Middle Aged, Molecular Sequence Data, Research Support; Non-U.S. Gov't, Somatic Hypermutation; Immunoglobulin/*genetics
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-92167DOI: 10.1016/j.leukres.2004.05.016PubMedID: 15607363OAI: oai:DiVA.org:uu-92167DiVA: diva2:165145