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.
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References
A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood. 1997;89:3909–3918.
Lee SS, Cho KJ, Kim CW, Kang YK. Clinicopathological analysis of 501 non-Hodgkin’s lymphomas in Korea according to the revised European-American classification of lymphoid neoplasms. Histopathology. 1999;35:345–354.
The World Health Organization classification of malignant lymphomas in Japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists. Pathol Int. 2000;50:696–702.
Kuppers R, Dalla-Favera R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene. 2001;20:5580–5594.
Jaffe SJ, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC; 2001.
Pileri SA, Dirnhofer S, Went P, et al. Diffuse large B-cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification. Histopathology. 2002;41:482–509.
Lossos IS, Levy R. Diffuse large B-cell lymphoma: insights gained from gene expression profiling. Int J Hematol. 2003;77:321–329.
Yamaguchi M, Seto M, Okamoto M, et al. De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients. Blood. 2002;99:815–821.
Katzenberger T, Lohr A, Schwarz S, et al. Genetic analysis of de novo CD5+ diffuse large B-cell lymphomas suggests an origin from a somatically mutated CD5+ progenitor B cell. Blood. 2003;101:699–702.
Karnan S, Tagawa H, Suzuki R, et al. Analysis of chromosomal imbalances in de novo CD5-positive diffuse large-B-cell lymphoma detected by comparative genomic hybridization. Genes Chromosomes Cancer. 2004;39:77–81.
Nakamura N, Hashimoto Y, Kuze T, et al. Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive diffuse large B-cell lymphoma. Lab Invest. 1999;79:925–933.
Nakamura N, Kuze T, Hashimoto Y, et al. Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma. Leukemia. 2001;15:452–457.
Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94:1840–1847.
Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94:1848–1854.
Walsh SH, Thorselius M, Johnson A, et al. Mutated VH genes and preferential VH3-21 use define new subsets of mantle cell lymphoma. Blood. 2003;101:4047–4054.
Kienle D, Krober A, Katzenberger T, et al. VH mutation status and VDJ rearrangement structure in mantle cell lymphoma: correlation with genomic aberrations, clinical characteristics, and outcome. Blood. 2003;102:3003–3009.
Lossos IS, Okada CY, Tibshirani R, et al. Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas. Blood. 2000;95:1797–1803.
Nakamura N, Abe M. Histogenesis of CD5-positive and CD5-negative B-cell neoplasms on the aspect of somatic mutation of immunoglobulin heavy chain gene variable region. Fukushima J Med Sci. 2003;49:55–67.
Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103:275–282.
Nollet F, Cauwelier B, Billiet J, et al. Do B-cell chronic lymphocytic leukemia patients with Ig VH3-21 genes constitute a new subset of chronic lymphocytic leukemia? Blood. 2002;100:1097–1098.
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Nakamura, N., Nakamura, S., Yamaguchi, M. et al. CD5+ Diffuse Large B-Cell Lymphoma Consists of Germline Cases and Hypermutated Cases in the Immunoglobulin Heavy Chain Gene Variable Region. Int J Hematol 81, 58–61 (2005). https://doi.org/10.1532/IJH97.04119
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DOI: https://doi.org/10.1532/IJH97.04119