Immunoglobulin Gene Mutations and Frequent Use of VH1-69 and VH4-34 Segments in Hepatitis C Virus-Positive and Hepatitis C Virus-Negative Nodal Marginal Zone B-Cell Lymphoma

Abstract

Nodal marginal zone B-cell lymphoma (NMZL) is actually considered as a distinct entity that must be

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

“…The first one is related to chronic antigenic stimulation with biological auto-immunity (RF and MC) leading to MZL [29,30], which as a result of secondary genetic events, may subsequently evolve towards transformed DLBCL. In de novo DLBCL we could hypothesise that a pro-tumour favourable environment can lead to B cell transformation [31] or that direct HCV infection of B cell may induce transformation [24].…”

Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas

“…Anti-HCV antibodies, the monoclonal compound of type II cryoglobulinemia and the lymphoma's immunoglobulins were found to be part of the same phenomenon, that is, the immunological response to HCV antigens. [21][22][23][24][25][26][27][28] Moreover, interaction between the virus and the cell surface activates STAT3 and leads to cellular transformation. 29 Finally, recent research showed that tumoral HCV-infected B cells have an increased rate of mutations of IgH, BCL-6, P53 and b-catenin.…”

1086 IGHV1-69 as a Promising Candidate for the Development of a Shared Immunotherapy to B-cell Lymphomas

“…Sequence analysis of the rearranged V H segments in these tumors revealed a substantial deviation from the germline V H 1-69 sequence with a degree of mutations very similar among the different cases of lymphoma [61].…”

“…Six samples were kindly provided by Prof. Salvatore De Vita and Dr. Martina Fabris (Clinic of Rheumatology, DSMB, University of Udine, Italy), 10 by Dr. Valter Gattei (Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, PN, Italy), 6 by Dr. Massimo Di Nicola ("C. Gandini" Medical Oncology, Bone Marrow Transplantation Unit; Fondazione I.R.C.C.S., Istituto Nazionale per lo Studio e la Cura dei Tumori, National Cancer Institute, Milan, Italy), and 1 was collected at the Centro di Riferimento Oncologico, National Cancer Institute (I.R.C.C.S., Aviano, PN, Italy). IGHV1-69 expression was determined by sequencing of IGHV amplicons derived from either reversetranscribed total RNA or genomic DNA [28,61]. Buffy coats from 51 healthy donors were also collected and included in this study.…”

“…Gastric MALT inflammation-dependent tumors frequently used V H 3-23 and V H 3-30 fragments, which have been closely associated also with autoimmune diseases. Indeed, they have been frequently used in thymic MALT lymphoma, a tumor closely associated with autoimmune disease [59]; while salivary MALT lymphomas B-cells mainly express V H 1-69 [60].Some papers revealed also the shared use of a specific Ig rearrangement in different lymphoma histotypes, as for example the expression of V H 4-34 frequently found in diffuse large-cell lymphoma, primary central nervous system lymphoma, B-chronic lymphocytic leukemia (CLL), and autoimmune disorders, and expressed in about 5% of healthy adult B lymphocytes [61].In CLL, the mutational status of the immunoglobulin genes expressed in tumor B-cells can be used to segregate patients into 2 subsets that have significantly different rates of disease progression: the unmutated VH genes are associated with a greater tendency for disease progression and shorter survival than the mutated ones. Within the unmutated group several studies revealed that the Ig repertoire shows a reduce variability compared with that of adult blood B cells, with a frequent use of V H 1-69, V H 3-07, V H 3-21, and V H 4-34, and a skewed D3-3 and J6 gene usage with restricted reading frames (RFs) in particularly linked to the V H 1-69 expression [30,31].…”