Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted Vλ2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope

Tobin, Gerard; Thunberg, Ulf; Johnson, Anna; Eriksson, Inger; Söderberg, Ola; Karlsson, Karin; Merup, Mats; Juliusson, Gunnar; Vilpo, Juhani; Enblad, Gunilla; Sundström, Christer; Roos, Göran; Rosenquist, Richard

doi:10.1182/blood-2002-11-3485

Cited by 279 publications

(319 citation statements)

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“…VH3-23 and VH3-30 have been closely associated with autoimmune disease, with the former found in patients with autoimmune thrombocytopenia, 28,29 Graves' disease, 30 and Wegener's granulomatosis, 31 and the latter in patients with systemic lupus erythematosus, 29 autoimmune thrombocytopenia, 28 and Kawasaki's disease. 32 In contrast, a biased usage of particular VH fragments has been reported in chronic lymphoid leukemia (VH3-21), 14,15 splenic marginal zone lymphoma (VH1-2), 16 and salivary MALT lymphoma (VH1-69). 17 We have reported recently that VH3-23 and VH3-30 have been frequently used in thymic MALT lymphoma, a tumor closely associated with autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

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Immunoglobulin VH gene analysis in gastric MALT lymphomas

et al. 2007

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The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are successfully treated with Helicobacter pylori eradication alone. However, certain subsets of these tumors are resistant to the eradication treatment. As API2-MALT1 fusion is a feature of one of these subsets, we divided gastric MALT lymphomas into three groups: eradication-responsive and API2-MALT1 fusion-negative (Group A), eradication-resistant and fusion-negative (Group B), and eradication-resistant and fusion-positive (Group C). To characterize further gastric MALT lymphomas, we analyzed VH genes, which do not change in the course of tumor progression, by extensive subcloning of the monoclonal PCR products of 45 cases. VH3-23 and VH3-30 were preferentially used in Group A tumors (14/23 cases, 61%) as compared with Group B (1/10 cases, 10%, P ¼ 0.0094) and Group C (2/ 12 cases, 17%, P ¼ 0.017). Tumors of Groups B and C used variegated VH fragments, and no dominant VH fragments were noted. Somatic mutation was detected in most of the cases. Ongoing mutation was detected in 3/45 cases (7%), when assessed according to strict criteria for a confirmed mutation. These findings suggest that inflammation-dependent tumors (Group A) may be derived from a highly restricted, probably H. pyloriassociated, B cell subset and may not often progress to those that are inflammation-independent (Groups B and C). Although considered to be common in this tumor, ongoing mutation may be infrequent when assessed by strict criteria. Keywords: gastric MALT lymphoma; helicobacter pylori; eradication; immunoglobulin heavy chain variable genes; API2-MALT1 fusion gene Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct low-grade lymphoma, which is typically localized long term at the site of origin. 1 A preexisting chronic inflammation, such as Helicobacter pylori gastritis, Hashimoto's thyroiditis, or Sjogren's syndrome is considered to influence significantly its development. 1 The etiological link between gastric MALT lymphoma and H. pylori gastritis has arisen from the fact that the majority of gastric MALT lymphomas (approximately 70% of cases) show complete regression on eradication of H. pylori alone. 2 API2-MALT1 fusion, cloned from t(11;18)(q21;q21), is a gene alteration specific to MALT lymphomas. 3,4 API2 is a member of the IAP (inhibitor of apoptosis) gene family, and is essential for the suppression of apoptosis. 5 MALT1, a novel

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Section: Discussionmentioning

confidence: 99%

“…12,13 A biased usage of particular VH segments has been reported in chronic lymphoid leukemia, 14,15 splenic marginal zone lymphoma, 16 and MALT lymphomas of the salivary gland 17 and thymus. 18 Although gastric MALT lymphoma has been studied more intensively than MALT lymphomas in other sites, its VH gene usage has not been well characterized.…”

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confidence: 99%

Immunoglobulin VH gene analysis in gastric MALT lymphomas

et al. 2007

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“…In Ig-unmutated B-CLL, biased usage of the V H 1-69 gene has been shown by several groups in a significant fraction of patients. 2,[5][6][7][8][9][10][11] Lately, small subsets of V H 1-69 ϩ cases with more or less identical heavy-and light-chain Ig rearrangement features have also been reported. 12,13 These findings have led to the speculation that unknown antigens could be involved in the pathogenesis of V H 1-69 ϩ B-CLL.…”

Section: Introductionmentioning

confidence: 99%

“…10 Interestingly, V H 3-21-utilizing patients showed short overall survival, similar to patients with unmutated V H genes, despite the fact that 2-thirds of them had mutated V H genes. 10,11,14,15 Furthermore, many of these V H 3-21 ϩ rearrangements (both mutated and unmutated) displayed unusually short and highly homologous complementarity-determining regions 3 (CDR3s), predominant light chain expression, and restricted use of 1 particular V gene, V 2-14. 11 These latter findings have implicated that an unknown antigen epitope could be recognized by the homologous V H 3-21 ϩ /V 2-14 ϩ BCRs expressed in the different V H 3-21 ϩ tumors.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] The selection of V H genes has been shown to be a nonrandom process in B-CLL with overrepresentation of the V H 1-69, V H 3-7, V H 3-21, and V H 4-34 genes. 2,[5][6][7][8][9][10][11] The implication of preferential V H gene usage has been hypothesized to be a result of antigen selection of B cells with certain B-cell receptors (BCRs), which then might render a higher probability to undergo malignant transformation. In Ig-unmutated B-CLL, biased usage of the V H 1-69 gene has been shown by several groups in a significant fraction of patients.…”

Section: Introductionmentioning

confidence: 99%

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