Is there a role for antigen selection in mantle cell lymphoma?: Immunogenetic support from a series of 807 cases
2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 11, 3088-3095 p.Article in journal (Refereed) Published
We examined 807 productive IGHV-IGHD-IGHJ gene rearrangements from mantle cell lymphoma (MCL) cases, by far the largest series to date. The IGHV gene repertoire was remarkably biased, with IGHV3-21, IGHV4-34, IGHV1-8, and IGHV3-23 accounting for 46.3% of the cohort. Eighty-four of 807 (10.4%) cases, mainly using the IGHV3-21 and IGHV4-34 genes, were found to bear stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences and were placed in 38 clusters. Notably, the MCL stereotypes were distinct from those reported for chronic lymphocytic leukemia. Based on somatic hypermutation (SHM) status, 238/807 sequences (29.5%) carried IGHV genes with 100% germ line identity; the remainder (569/807; 70.5%) exhibited different SHM impact, ranging from minimal (in most cases) to pronounced. Shared replacement mutations across the IGHV gene were identified for certain subgroups, especially those using IGHV3-21, IGHV1-8, and IGHV3-23. Comparison with other entities, in particular CLL, revealed that several of these mutations were "MCL-biased." In conclusion, MCL is characterized by a highly restricted immunoglobulin gene repertoire with stereotyped VH CDR3s and very precise SHM targeting, strongly implying a role for antigen-driven selection of the clonogenic progenitors. Hence, an antigen-driven origin of MCL could be envisaged, at least for subsets of cases.
Place, publisher, year, edition, pages
2011. Vol. 118, no 11, 3088-3095 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-159465DOI: 10.1182/blood-2011-03-343434ISI: 000294955900026OAI: oai:DiVA.org:uu-159465DiVA: diva2:445555