Immunoarchitectural patterns in splenic marginal zone lymphoma: correlations with chromosomal aberrations, <i><scp>IGHV</scp></i> mutations, and survival. A study of 76 cases

Traverse-Gléhen, Alexandra; Bachy, Emmanuel; Baseggio, Lucile; Callet‐Bauchu, Evelyne; Gazzo, Sophie; Verney, Aurélie; Hayette, Sandrine; Jallades, Laurent; Ffrench, Martine; Salles, Gilles; Felman, Pascale; Berger, Françoise

doi:10.1111/his.12092

Cited by 13 publications

(3 citation statements)

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“…[3][4][5] Such mutations have been identified in both the B-cell Receptor (BCR) and Toll-Like Receptor (TLR) signaling pathways e.g. CARD11 and MYD88 gene mutations, respectively, 3,[5][6][7][8][9] implicating immune signaling in the natural history of selected SMZL cases. This claim is also supported by the particularly skewed immunoglobulin heavy variable (IGHV) gene repertoire in SMZL, where a substantial proportion of cases (from 20% to more than 30%, depending on the series) express a single IGHV gene allele, namely IGHV1-2*04, suggesting (super)antigenic pressure on the malignant clone involving inflammatory/infectious agents.…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o nadaptor molecule MyD88 connects distinct TLRs to proximal IRAK kinases which then trigger a cascade of phosphorylation events, eventually leading to MAPK and IKK activation and the induction of specific transcriptional programs including that of the NF-κB complex. 16 With all the above in mind, we herein aimed at characterizing TLR expression and function in SMZL, in order to assess the potential impact of TLR signaling on the biology of this disease. Methods Cell purificationBlood and tissue samples were obtained from SMZL patients after informed consent as part of a study (ViVi-NHL) approved by the institutional ethics committee. SMZL cells were negatively selected and purified using a B-cell enrichment kit (RosetteSep; StemCell Technologies) following the manufacturer's instructions. Normal B cells were purified by negative selection (EasySep; StemCell Technologies) from buffy coats. Preparations were virtually devoid of NK cells, T-lymphocytes and monocytes.In 19 SMZL cases, total peripheral blood mononuclear cells (PBMC) were isolated by Ficoll gradient centrifugation without further purification (the percentage of CD19 + cells in these cases is reported in Online Supplementary Table S1). In all cases, subsequent flow cytometric analyses were performed after gating on CD19+ cells. TLR expression analysisSMZL cells were analyzed either at the time of blood withdrawal or after thawing. The analysis was performed by flow cytometry using the following antibodies: anti-TLR1 and anti-TLR7 (AbCam); anti-TLR2 (Invitrogen); anti-TLR6 and anti-TLR10 (IMGENEX); anti-TLR8 (DENDRITICS), and anti-TLR9 (eBiosciences). The BD Cytofix/Cytoperm reagent was used for the intracellular staining of TLR7, TLR8 and TLR9. Antibodies against IgD, IgM, CD38 and CD19 were used to detect normal MZ B cells in spleen samples, as previously described. 7-AminoActinomycin D (7-AAD, BD Pharmingen™) was used for the exclusion of nonviable cells in flow cytometric assays. All flow cytometric analyses were performed on a FC-500 (Beckman Coulter) or on a FACSAria II (Becton Dickinson). Cell culture and functional studiesSMZL cells were either unstimulated or stimulated with specific TLR ligands (Online Supplementary Methods). Collection was performed either after 24 hours for CD86 (BD Pharmingen) and CD25 (Beckman Coulter) flow cytometry analysis, or after 48 hours to assess cell proliferation (Ki67 staining, BD Biosciences), apoptosis (Annexin V and Propidium Iodide, Bender Med Systems) and viability (CellTiter-Glo Luminescent Cell Viability Assay, Promega). The IRAK1/4 inhibitor I (Sigma) was used at the concentration of 3 μM 30 minutes before TLR stimulation. The MyD88 inhibitory peptide and control peptide (Novus Biologicals) were used at the concentration of 100 μM. Molecular studiesi. Immunogenetic analysis. PCR amplification and sequence analysis of IGHV-IGHD-IGHJ gene rearrangements was performed as previously described. 20 ii. Qualitative assessment of TLR1-10 and TIR8 expression b...

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Section: Introductionmentioning

confidence: 99%

Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation

et al. 2015

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“…It is expected that SMZL derives from a marginal zone B-cell with possible previous antigen exposure. The rearrangements of the immunoglobulin genes found in 30% of SMZL cases may suggest that this tumor derives from a highly selected B-cell population [ 34 , 35 , 36 , 37 ]. The initial hypothesis was, indeed, that SMZL derived from marginal zone B cells due to a histological marginal zone differentiation in splenic specimens [ 34 , 38 ] and the use of a limited repertoire, with a preferential usage of specific IGHV genes, such as IGHV1-2*04 (31%), IGHV3-23 (8%), and IGHV4-34 (13%).…”

Section: Resultsmentioning

confidence: 99%

“…The initial hypothesis was, indeed, that SMZL derived from marginal zone B cells due to a histological marginal zone differentiation in splenic specimens [ 34 , 38 ] and the use of a limited repertoire, with a preferential usage of specific IGHV genes, such as IGHV1-2*04 (31%), IGHV3-23 (8%), and IGHV4-34 (13%). In addition, approximately 10% of cases express B-cell receptors (BCRs) with quasi-identical IGHV sequences, including the antigen-binding site, strongly suggesting that antigen selection might contribute to the lymphomagenesis of SMZL [ 36 , 39 ]. Moreover, Warsame et al reported that SMZL with an HV1-2 rearrangement is not associated with hepatitis C virus infection and produced poly- and self-reactive antibodies [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas

et al. 2021

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Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as immuno-chemotherapy or splenectomy, with all associated side effects. In recent years, advances in the comprehension of SMZL physiopathology have multiplied, thanks to the arrival of new devices in the panel of available molecular biology techniques, allowing the discovery of new molecular findings. In the era of targeted therapies, an update of current knowledge is needed to guide future researches, such as those on epigenetic modifications or the microenvironment of these lymphomas.

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Mature B‐ and T‐cell neoplasms and Hodgkin lymphoma

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Aukema

2015

Cancer Cytogenetics

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Immunoarchitectural patterns in splenic marginal zone lymphoma: correlations with chromosomal aberrations, IGHV mutations, and survival. A study of 76 cases

Abstract: We report the histological spectrum of SMZL, and discuss the differential diagnosis and requirement for molecular and cytogenetic analysis in atypical cases.

Cited by 13 publications

References 39 publications

Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation

Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation

New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas

Mature B‐ and T‐cell neoplasms and Hodgkin lymphoma

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