New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas.
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ABSTRACT:
SUBMITTER: Donzel M
PROVIDER: S-EPMC8482189 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Splenic marginal zone lymphomas (SMZL) are an uncommon type of B-cell non-Hodgkin's lymphoma (NHL-B) in which no specific chromosomal translocations have been described. In contrast, the most frequent cytogenetic abnormality is the loss of the long arm of chromosome 7 (7q). Previous reports have located this loss in the 7q32 region. In order to better characterize the genomic imbalances in SMZL, molecular studies were carried out in 73 patients with SMZL. To gain insight into the mapping at 7q a tiling array was also used. The results confirmed the loss of 7q as the most frequent change. In addition, several abnormalities, including 4q22.1, 1q21.3-q22, 6q25.3, 20q13.33, 3q28, 2q23.3-q24.1 and 17p13, were also present. A loss of 7q22.1 at 99925039-101348479 bp was observed in half of the cases. The region of 7q22.1 has not previously been characterised in SMZL. Our results confirmed the presence of a new region of loss on chromosome 7 in these NHL.
| S-EPMC3177857 | biostudies-literature
Project description:Splenic marginal zone lymphomas (SMZLs) have been proposed to originate from postgerminal center memory B cells that usually have mutated immunoglobulin heavy-chain variable (VH) genes. However, the majority of SMZLs are thought to express both IgD and IgM, which is more typical of naïve B cells that have unmutated VH genes. To better define the SMZL cell of origin and pathogenesis, we studied the histological and immunophenotypic features of eight cases and also sequenced their rearranged VH genes. Half of the cases had unmutated VH genes consistent with a naïve B-cell origin and half had mutated VH genes consistent with a memory B-cell origin. Most of the unmutated cases (three of four) were positive for IgD, which further supports a naïve B-cell origin, whereas the others were negative. In addition, VH gene segment use seems to be nonrandom because seven of eight cases used genes from the VH1 or VH4 families and repetitive use of the V1-2, V1-69, and V4-34 gene segments was observed. Our results suggest there are two types of SMZLs, one that originates from naïve marginal zone B cells in addition to one that originates from memory marginal zone B cells, and that antigen selection may be occurring during lymphomagenesis.
| S-EPMC1850701 | biostudies-literature
Project description:Marginal zone lymphomas (MZLs) represent about 7% of B-cell non-Hodgkin lymphomas and include 3 different subtypes-namely, extranodal (EMZL), nodal, and splenic (SMZL). The initial assessment requires specific diagnostic and staging procedures depending on organ-related peculiarities. In particular, although positron emission tomography/computed tomography was not initially recommended, recent data have reassessed its role in the routine staging of MZL, especially when only localized treatment is planned or there is a suspicion of histologic transformation. Recent findings have improved the risk stratification of MZL patients, highlighting the association of early progression after frontline therapy with worse overall survival. A significant fraction of MZL cases may be related to specific bacterial (ie, Helicobacter pylori in gastric EMZL) or viral infections (hepatis C virus), and in the earlier phases of disease, a variable percentage of patients may respond to anti-infective therapy. Involved-site radiotherapy has a central role in the management of localized EMZL not amenable to or not responding to anti-infective therapy. Although rituximab-based treatments (bendamustine- rituximab in advanced EMZL or rituximab monotherapy in SMZL) have demonstrated favorable results, the current therapeutic scenario is predicted to rapidly change as emerging novel agents, especially Bruton's tyrosine kinase inhibitors, have demonstrated promising efficacy and safety profiles, leading to their approval in the relapsed setting. Moreover, a large variety of novel agents (phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cells, bispecific antibodies) are being tested in MZL patients with encouraging preliminary results.
| S-EPMC9901419 | biostudies-literature
Project description:The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and approximately 30% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a "global" NF-?B negative regulator, in 1 of 12 splenic marginal zone lymphomas. To investigate further whether deregulation of the NF-?B pathway plays a role in the pathogenesis of splenic marginal zone lymphoma, we screened several NF-?B regulators for genetic changes by PCR and sequencing. Somatic mutations were found in A20 (6/46=13%), MYD88 (6/46=13%), CARD11 (3/34=8.8%), but not in CD79A, CD79B and ABIN1. Interestingly, these genetic changes are largely mutually exclusive from each other and MYD88 mutation was also mutually exclusive from 7q deletion. These results strongly suggest that deregulation of the TLR (toll like receptor) and BCR (B-cell receptor) signaling pathway may play an important role in the pathogenesis of splenic marginal zone lymphoma.
| S-EPMC3347666 | biostudies-literature
Project description:The t(11;18)(q21;q21) is thought to represent an important primary event in the development of marginal zone lymphomas, although an accurate estimation of the frequency and distribution of this genetic alteration among nodal, splenic, and extranodal marginal zone lymphoma types has yet to be determined. Recently, molecular genetic studies have shown that this translocation results in the fusion of the API2 gene on chromosome 11 and a novel gene termed MALT1 on chromosome 18. To investigate the incidence of API2-MALT1 fusion transcripts among marginal zone lymphomas and to determine possible marginal zone lymphoma subtype associations, we used reverse transcriptase-polymerase chain reaction to analyze RNAs extracted from frozen tissue samples of 99 marginal zone lymphomas. Fifty-seven involved diverse extranodal sites including 14 stomach, 11 lung, 7 orbit, 7 parotid, 5 thyroid, 5 lacrimal gland, 3 small intestine, 2 large intestine, 1 kidney, 1 paraspinal region and 1 skin. Twenty-one primary splenic and twenty-one primary nodal marginal zone lymphomas were also studied. API2-MALT1 fusion transcripts were detected in 12 of 57 extranodal marginal zone lymphomas (21%), but in none of the nodal or splenic cases. The cDNA sequences of the fusion transcripts were determined, revealing variation in the coding sequence fusion point for both API2 and MALT1. The findings suggest that t(11;18)(q21;q21) is restricted to extranodal marginal zone lymphomas and that these tumors have distinct genetic etiologies in comparison with their splenic and nodal counterparts.
| S-EPMC1876902 | biostudies-literature
Project description:Splenic marginal zone lymphoma (SMZL) is a rare chronic B lymphoproliferative disease, whose molecular pathogenesis is still not well established. For the first time a proteomic approach was undertaken to analyse the protein profiles of SMZL tissue. Western blot, immunohistochemical analysis and functional data mining were also performed in order to validate results, classify proteins, and explore their potential relationships. We demonstrated that SMZL is characterized by modulation of proteins related to energetic metabolism and apoptosis pathways. We also reported specific proteins (such as biliverdin reductase A, manganese superoxide dismutase, beta-2 microglobulin, growth factor receptor-bound protein 2, acidic leucine-rich nuclear phosphoprotein 32 family member A, and SET nuclear oncogene) directly involved in NF-kBand BCR pathways, as well as in chromatin remodelling and cytoskeleton. Our findings shed new light on SMZL pathogenesis and provide a basis for the future development of novel biomarkers.
2015-04-23 | PXD001124 | Pride
Project description:Purpose: Single cell RNA-Seq was used to characterize in depth splenic samples obtained from splenic marginal zone lymphomas Methods: 3 frozen samples of spleen from SMZL patients were selected and thawed for performing a 10X genomics single cell RNA-Sequencing 3' assay. Results: Tumor cells formed mainly patient specific-B cell clusters, while T-cells from the 3 patients clustered together. Conclusion: Single RNA-Seq unveils the cellular composition of splenic tumors from SMZL patients.
2021-10-31 | GSE175785 | GEO
Project description:Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappa B, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease entity. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal (EMZL), nodal (NMZL) and splenic (SMZL) MZLs. Inactivating mutations encoding truncated A20 proteins were identified in 6/32 (18.8%) MZLs, including 3/11 (27.3%) EMZLs, 2/9 (22.2%) NMZLs, and 1/12 (8.3%) SMZLs. Two additional unmutated non-splenic MZLs also showed mono- or biallelic A20 deletions by FISH and/or array-CGH. Thus, A20 loss by both somatic mutations and/or deletions represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappa B activation. Keywords: Genome variation profiling by SNP array
2009-04-01 | GSE13989 | GEO
Project description:The dura is a rare site of involvement by marginal zone lymphoma (MZL) and the biology of dural MZL is not well understood. We performed genome-wide DNA copy number and targeted mutational analysis of 14 dural MZL to determine the genetic landscape of this entity. Monoallelic and biallelic inactivation of TNFAIP3 by mutation (n=5) or loss (n=1) was observed in 6/9 (67%) dural MZL exhibiting plasmacytic differentiation, including 3 IgG4+ cases. In contrast, activating NOTCH2 mutations were detected in 4/5 (80%) dural MZL displaying variable monocytoid morphology. Inactivating TBL1XR1 mutations were identified in all NOTCH2 mutated cases. Recurrent mutations in KLHL6 (n=2) and MLL2 (n=2) were also detected. Gains at 6p25.3 (n=2) and losses at 1p36.32 (n=3) were common chromosomal imbalances, with loss of heterozygosity (LOH) of these loci observed in a subset of cases. Translocations involving the IGH or MALT1 genes were not identified. Our results indicate genetic similarities between dural MZL and other MZL subtypes. However, recurrent and mutually exclusive genetic alterations of TNFAIP3 and NOTCH2 appear to be associated with distinct disease phenotypes in dural MZL.
| S-EPMC5190007 | biostudies-other
Project description:Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappa B, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease entity. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal (EMZL), nodal (NMZL) and splenic (SMZL) MZLs. Inactivating mutations encoding truncated A20 proteins were identified in 6/32 (18.8%) MZLs, including 3/11 (27.3%) EMZLs, 2/9 (22.2%) NMZLs, and 1/12 (8.3%) SMZLs. Two additional unmutated non-splenic MZLs also showed mono- or biallelic A20 deletions by FISH and/or array-CGH. Thus, A20 loss by both somatic mutations and/or deletions represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappa B activation. Keywords: Genome variation profiling by SNP array 27 MZL samples. No technical replications.
2009-04-01 | E-GEOD-13989 | biostudies-arrayexpress