ArticleBlood2022
Aberrant expansion of spontaneous splenic germinal centers induced by hallmark genetic lesions of aggressive lymphoma.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- BCR signal strength governs VH gene replacement in peripheral B cells.Cellular & molecular immunology · 2026Article
- Genetically driven immune microenvironment states associate with therapeutic responses in MYD88 mutant lymphomas.Molecular cancer · 2026Article
- Molecular Pathogenesis and Therapeutic Response of Diffuse Large B Cell Lymphoma Genetic Subtypes.Annual review of cancer biology · 2026Article
- Mouse models of B cell lymphomas on the basis of genetic features.Frontiers in immunology · 2026Review
- Common origins of autoimmune diseases and lymphoid malignancies.Trends in immunology · 2025Review
- Review
- Gα13 restricts nutrient driven proliferation in mucosal germinal centers.Nature immunology · 2024Article
- Molecular targets of glucocorticoids that elucidate their therapeutic efficacy in aggressive lymphomas.Cancer cell · 2024Article
- An inducible Cd79b mutation confers ibrutinib sensitivity in mouse models of Myd88-driven diffuse large B-cell lymphoma.Blood advances · 2024Article
- Leukemic presentation and progressive genomic alterations of MCD/C5 diffuse large B-cell lymphoma (DLBCL).Cold Spring Harbor molecular case studies · 2023Article
- Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas.Cancer discovery · 2023Article
- An Aged/Autoimmune B-cell Program Defines the Early Transformation of Extranodal Lymphomas.Cancer discovery · 2023Article
- Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies.Blood cancer discovery · 2023Article
- Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies.Blood cancer discovery · 2023Article
- Mouse models of diffuse large B cell lymphoma.Frontiers in immunology · 2023Review
- NF-κB Mutations in Germinal Center B-Cell Lymphomas: Relation to NF-κB Function in Normal B Cells.Biomedicines · 2022Review
- MCD-DLBCL arises from germinal center B cells.Blood · 2022Article
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15 authors at 4 institutions in 3 countries.
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Abstract
Unique molecular vulnerabilities have been identified in the aggressive MCD/C5 genetic subclass of diffuse large B-cell lymphoma (DLBCL). However, the premalignant cell-of-origin exhibiting MCD-like dependencies remains elusive. In this study, we examined animals carrying up to 4 hallmark genetic lesions found in MCD consisting of gain-of-function mutations in Myd88 and Cd79b, loss of Prdm1, and overexpression of BCL2. We discovered that expression of combinations of these alleles in vivo promoted a cell-intrinsic accumulation of B cells in spontaneous splenic germinal centers (GCs). As with MCD, these premalignant B cells were enriched for B-cell receptors (BCRs) with evidence of self-reactivity, displayed a de novo dependence on Tlr9, and were more sensitive to inhibition of Bruton's tyrosine kinase. Mutant spontaneous splenic GC B cells (GCB) showed increased proliferation and IRF4 expression. Mice carrying all 4 genetic lesions showed a >50-fold expansion of spontaneous splenic GCs exhibiting aberrant histologic features with a dark zone immunophenotype and went on to develop DLBCL in the spleen with age. Thus, by combining multiple hallmark genetic alterations associated with MCD, our study identifies aberrant spontaneous splenic GCBs as a likely cell-of-origin for this aggressive genetic subtype of lymphoma.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.