title: CD5+ diffuse large B-cell lymphoma consists of germline cases and hypermutated cases in the immunoglobulin heavy chain gene variable region.
abstract: CD5+ diffuse large B-cell lymphoma (DLBCL) has recently been identified as a subgroup with different clinical characteristics from CD5- DLBCL and as having a poorer outcome than CD5- DLBCL. Data regarding differences in gene alteration between CD5+ and CD5- DLBCL have accumulated. In this article, we report an analysis of the immunoglobulin heavy-chain gene variable region (VH) gene in 35 cases of CD5+ DLBCL and compare these cases with those with the germline of the VH gene (GL-VH) and those with a somatically hypermutated VH gene (HM-VH). When the CD5+ DLBCL cases were subdivided with a cutoff value of 98% homology in the VH gene, there were 7 cases (20%) of GL-VH and 28 cases (80%) of HM-VH. The proportion of GL-VH cases in CD5+ DLBCL was more than that in CD5 DLBCL. Although we found no significant difference in pretreatment clinical parameters between the GL-VH and HM-VH subgroups, there was a tendency for the GL-VH subgroup to show lower incidences of elevation of lactate dehydrogenase and >1 site of extranodal involvement compared to the HM-VH subgroup. The overall survival curve of the HM-VH subgroup showed a rapid decline followed by a plateau, whereas that of the GL-VH subgroup declined constantly after 5 years, suggesting that GL-VH disease may not be curable by standard therapies. These findings suggest that CD5+ DLBCL with GL-VH shares clinical features with mantle cell lymphoma, the cellular origin of which has been considered to be pre-germinal center B-cells. We therefore propose that analysis of the VH gene is important for predicting the clinical course of CD5+ DLBCL.
authors.affiliation: Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan. nao@fmu.ac.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Motoko
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Ryo
authors.initials: R
authors.lastname: Ichinohasama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kuze
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
mesh_terms: D018956:CD5 Antigens / Q000378:metabolism; D018095:Germ-Line Mutation; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D018956:CD5 Antigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
references.citation: Blood. 2004 Jan 1;103(1):275-82
references.pmid: 14504078
references.citation: Int J Hematol. 2003 May;77(4):321-9
references.pmid: 12774918
references.citation: Blood. 2002 Feb 1;99(3):815-21
references.pmid: 11806981
references.citation: Fukushima J Med Sci. 2003 Dec;49(2):55-67
references.pmid: 15065636
references.citation: Blood. 2003 Oct 15;102(8):3003-9
references.pmid: 12842981
references.citation: Histopathology. 1999 Oct;35(4):345-54
references.pmid: 10564389
references.citation: Blood. 2000 Mar 1;95(5):1797-803
references.pmid: 10688840
references.citation: Blood. 2003 Jan 15;101(2):699-702
references.pmid: 12393524
references.citation: Blood. 1999 Sep 15;94(6):1840-7
references.pmid: 10477712
references.citation: Oncogene. 2001 Sep 10;20(40):5580-94
references.pmid: 11607811
references.citation: Histopathology. 2002 Dec;41(6):482-509
references.pmid: 12460202
references.citation: Pathol Int. 2000 Sep;50(9):696-702
references.pmid: 11012982
references.citation: Blood. 1999 Sep 15;94(6):1848-54
references.pmid: 10477713
references.citation: Blood. 2002 Aug 1;100(3):1097-8; author reply 1098-9
references.pmid: 12130479
references.citation: Blood. 1997 Jun 1;89(11):3909-18
references.pmid: 9166827
references.citation: Leukemia. 2001 Mar;15(3):452-7
references.pmid: 11237070
references.citation: Genes Chromosomes Cancer. 2004 Jan;39(1):77-81
references.pmid: 14603444
references.citation: Lab Invest. 1999 Aug;79(8):925-33
references.pmid: 10462030
references.citation: Blood. 2003 May 15;101(10):4047-54
references.pmid: 12637326