0000000000050211

AUTHOR

David Oscier

showing 5 related works from this author

Distinctive Patterns of Intraclonal Diversification In IGHV1-2*04 Immunoglobulin Receptors of Patients with Splenic Marginal Zone Lymphoma: A of Ongo…

2011

Abstract Abstract 2638 We recently demonstrated that over 30% of cases with splenic marginal-zone lymphoma (SMZL) express distinctive immunoglobulin (IG) receptors that utilize a single polymorphic variant of the IGHV1-2 gene (IGHV1-2*04) and also exhibit restricted antigen-binding site motifs and precise targeting of somatic hypermutation (SHM). On these grounds, we proposed the existence of molecular subtypes of SMZL defined by immunogenetic analysis of the IG receptors with implications for selection by specific (super) antigenic element(s) in the development of at least a major subset of SMZL. In order to gain insight as to whether antigen involvement is relevant only prior to the malig…

GeneticsImmunologySomatic hypermutationCell BiologyHematologyComplementarity determining regionBiologymedicine.diseaseBiochemistryGermlineSubcloningmedicinebiology.proteinSplenic marginal zone lymphomaAntibodyIGHV@GeneBlood
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Over 30% of Patients with Splenic Marginal Zone Lymphoma Express Distinctive Antigen Receptors Utilizing a Single Immunoglogulin Variable Gene: Impli…

2010

Abstract Abstract 634 We systematically explored the immunoglobulin (IG) gene repertoire in 337 cases with splenic marginal-zone lymphoma (SMZL), by far the largest series yet. To resolve classification uncertainties, we included in the analysis only cases with a diagnosis of SMZL based on spleen histopathological findings or cases fulfilling the 2008 SBLG criteria (Matutes et al. Leukemia 2008). We here report that the IG heavy variable (IGHV) gene repertoire in SMZL is remarkably biased, with only three genes accounting for 45.8% of cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23: 8.1%, respectively), significantly extending previous similar observations. Particularly for the IGHV1-2 gen…

GeneticsImmunologyCell BiologyHematologyBiologymedicine.diseaseBiochemistryLymphomamedicine.anatomical_structureImmunologymedicineRed pulpSplenic marginal zone lymphomaAlleleFramework regionIGHV@GeneDominance (genetics)
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Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications.

2012

We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele *04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2*04 peaked at 31%. The IGHV1-2*04 rearrangements carried significantly lo…

Immunoglobulin geneModels MolecularCancer ResearchGenes Immunoglobulin Heavy ChainGene Rearrangement B-Lymphocyte Heavy ChainImmunoglobulin Variable RegionSomatic hypermutationSplenic NeoplasmBiologyCohort StudiesantigenmedicineHumansSplenic marginal zone lymphomaAlleleGeneticsSplenic Neoplasmssplenic marginal-zone lymphomaHematologyGene rearrangementLymphoma B-Cell Marginal Zonemedicine.diseasePrognosisComplementarity Determining Regionssomatic hypermutationimmunoglobulin geneOncologyMutationIGHDsplenic marginal-zone lymphoma; immunoglobulin gene; somatic hypermutation; CDR3; antigenCDR3IGHV@Leukemia
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Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics

2016

NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) a…

0301 basic medicineLymphoid TissueScienceB-cell receptorReceptors Antigen B-CellGeneral Physics and AstronomySykKaplan-Meier EstimateBiologyArticleGeneral Biochemistry Genetics and Molecular BiologyNKX2-303 medical and health sciencesChemokine receptorstomatognathic systemLYNhemic and lymphatic diseasesmedicineAnimalsHumansSyk KinaseLymphocytesPhosphorylationB cellHomeodomain ProteinsMice KnockoutCàncer -- Aspectes molecularsMultidisciplinaryCell adhesion moleculeKinaseGene Expression ProfilingQLymphoma B-Cell Marginal ZoneGeneral Chemistryrespiratory system3. Good healthMice Inbred C57BL030104 developmental biologymedicine.anatomical_structureembryonic structurescardiovascular systemCancer researchCell Adhesion MoleculesProteïnesSignal TransductionTranscription FactorsNature Communications
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Splenic Marginal Zone Lymphoma Shows a Distinct Pattern of DNA Copy Number Aberrations That Correlates with Tumor Characteristics and Predicts Diseas…

2006

Abstract Splenic marginal zone lymphoma (SMZL) is an indolent B cell malignancy whose diagnosis is based on lymphocyte morphology, immunophenotype and marrow and/or splenic histology. Unlike other lymphomas, there is not a common chromosomal translocation specific for SMZL, and genetic prognostic factors are poorly defined. To investigate the pattern of genomic aberrations in SMZL, we applied comparative genomic hybridization to BAC microarrays (array CGH) to a well characterized series of 75 SMZL specimens. We applied two different 1 Mb-resolution BAC arrays: UCSF HumArray 3.2 and a novel array CGH platform developed at Univ. of Salamanca. These arrays allowed us to detect DNA copy number …

Tissue microarrayImmunologyFollicular lymphomaCell BiologyHematologyBiologymedicine.diseaseBiochemistryMolecular biologyLymphomaImmunophenotypingComplex KaryotypemedicineMantle cell lymphomaSplenic marginal zone lymphomaComparative genomic hybridizationBlood
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