Immunoglobulin Gene Mutation Patterns And Heterogeneity Of Marginal Zone Lymphoma Pdf

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The precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma NMZL remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning.

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Blood ; 17 : — Nodal marginal zone lymphoma NMZL is a rare form of indolent small B-cell lymphoma which has only been clearly identified in the last 2 decades and which to date remains incurable. Progress in therapeutic management has been slow, largely due to the very small number of patients treated and the heterogeneity of treatments administered; thus, standard-of-care treatment is currently nonspecific for this lymphoma entity. In this review, treatments routinely used to manage adult NMZL patients are presented, principally based on immunochemotherapy when treatment is needed.

Marginal zone B-cell lymphoma

The considerable heterogeneity in morphology, immunophenotype, genotype, and clinical behavior of splenic marginal zone lymphoma SMZL hinders firm conclusions on the origin and differentiation stage of the neoplastic cells. These results provide evidence for the diverse B-cell subpopulations residing in the SMZ, which could represent physiologic equivalents of distinct SMZL subtypes. The marginal zone of the human spleen SMZ is a microanatomical site at the border of the white and red pulp, mainly comprising of B cells, T cells, and macrophages. The SMZ appears especially well equipped for rapid humoral immune responses to blood-borne antigens. There is considerable evidence suggesting that responses to thymus independent type 2 antigens for example, bacterial capsular polysaccharides are dependent on the normal function of the splenic marginal zone 1 — 3. Human SMZ B cells are a heterogeneous population: evidence for this heterogeneity was provided by mutation analysis of rearranged immunoglobulin heavy IGH chain genes of microdissected SMZ cells as well as tonsillar marginal zone B cells equivalent to SMZ B cells 4 — 6 , which has demonstrated that some cells carried mutated IGHV genes while other cells carried unmutated genes. Importantly, however, the distribution of mutations was not always suggestive of selection by conventional T-dependent antigen.

Immunoglobulin Heavy-And Light-chain Repertoire in Splenic Marginal Zone Lymphoma

Patricia Algara, Marisol S. Piris; Analysis of the IgV H somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course. Blood ; 99 4 : — This study aimed to correlate the frequency of somatic mutations in the IgV H gene and the use of specific segments in the V H repertoire with the clinical and characteristic features of a series of 35 cases of splenic marginal zone lymphoma SMZL. The cases were studied by seminested polymerase chain reaction by using primers from the FR1 and J H region.

Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. Free to read. We studied the pattern of somatic hypermutation of the rearranged immunoglobulin heavy chain genes on 23 cases and have correlated these data with survival as well as immunophenotypic and genetic characteristics of the cases. Two-thirds of the cases show immunoglobulin gene mutations, half of which show evidence of antigen selection, whereas one-third of the cases show no significant mutations.

Marginal zone B-cell lymphomas , also known as marginal zone lymphomas MZLs , are a heterogeneous group of lymphomas that derive from the malignant transformation of marginal zone B-cells. MALT , the spleen , or lymph nodes. Mucosa-associated lymphoid tissue is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body such as the gastrointestinal tract , mouth , nasal cavity , pharynx , thyroid gland , breast , lung , salivary glands , eye , skin and the human spleen. However, NMZL carries a somewhat worse long term outcome than the other subtypes [1] and any of the MZL subtypes may progress in a low percentage of cases to a more aggressive lymphoma, particularly diffuse large B-cell lymphoma. Regardless of subtype, these EMZLs share similar pathophysiological i.

The clonotypic B cell receptor immunoglobulin BcR IG plays a seminal role in B cell lymphoma development and evolution. This clinical development complements immunogenetic evidence for antigen drive in the natural history of these tumors. Moreover, distinct entities display imprints of somatic hypermutation within the clonotypic BcR IG gene following patterns that strengthen the argument for antigen selection. Of note, at least in certain B cell lymphomas, the BcR IG genes are intraclonally diversified, likely in a context of ongoing interactions with antigen s.

Lebien , Fates of human 8-cell precursors , Blood , vol. Schwickert , ln vivo imaging of germinal centres reveals a dynamic open structure , Nature , issue. Lebien and T.

Blood ; 10 : — Nodal marginal zone lymphoma NMZL is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma SMZL by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL.

INTRODUCTION

The considerable heterogeneity in morphology, immunophenotype, genotype, and clinical behavior of splenic marginal zone lymphoma SMZL hinders firm conclusions on the origin and differentiation stage of the neoplastic cells. These results provide evidence for the diverse B-cell subpopulations residing in the SMZ, which could represent physiologic equivalents of distinct SMZL subtypes. Tags Type your tag names separated by a space and hit enter. Mol Med. Belessi C.

Javascript is currently disabled in your browser. Several features of this site will not function whilst javascript is disabled. Received 3 April Published 17 July Volume Pages 29—

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2 Response
  1. Varden V.

    Immunoglobulin Gene Mutation Patterns and Heterogeneity of Marginal Zone Beside the so-called extranodal B-cell MALT lymphoma, the splenic MZ.

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