ArticleBlood2022
Clonal germinal center B cells function as a niche for T-cell 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 43 papers.
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43 citing papers in PubMed, 52 citations in OpenAlex.
- RCLARITY: A Prospective Phase II Study of Rituximab Combined With Lenalidomide and Chidamide (RLC) for the Treatment of Relapsed/Refractory Angioimmunoblastic T-Cell Lymphoma.American journal of hematology · 2026Trial
- Different primary thyroid B-cell lymphomas show overlapping mutation profiles, suggesting involvement of a common pathogenic process.Haematologica · 2026Article
- TET2 as a Context-Dependent Epigenetic Integrator in Clonal Hematopoiesis, Inflammation, Cancer, and Immunotherapy.Cell biochemistry and function · 2026Review
- Article
- Clonal haematopoiesis in T-follicular helper cell lymphoma: A prognostic biomarker and early event in lymphoma evolution.British journal of haematology · 2026Article
- Integrated Single-Cell and Spatial Multi-Omics of Clonal Precursors and Immune Niches in Germinal Center Lymphomas.Cancers · 2026Article
- Unraveling the many faces of angioimmunoblastic T-cell lymphoma: clinical, pathological, and molecular heterogeneity.Annals of hematology · 2026Review
- Revealing tumor microenvironmental heterogeneity and prognostic value in angioimmunoblastic T-cell lymphoma via spatial transcriptome sequencing.Cell death & disease · 2026Article
- Born with two faces: sequential DLBCL, NOS and TFHL-AI withFrontiers in immunology · 2026Article
- Identification of a neoplastic Tfh-like cellular subset in a mouse model of angioimmunoblastic T cell lymphoma.Frontiers in oncology · 2026Article
- XPO1 inhibitor selinexor enhances the apoptotic effect of azacitidine in T-cell lymphoma with TET2/RHOA mutations via JAK3/STAT3 axis.Cell communication and signaling : CCS · 2025Article
- Integrating bulk and single-cell transcriptome to identify novel gene markers for germinal center B cells (GCB) subtype of diffuse large B-cell lymphoma.Annals of hematology · 2025Article
- Single-cell and spatial analysis reveals macrophage-T cell crosstalk in non-small cell lung cancer immunosuppression.Translational lung cancer research · 2025Article
- Integrating genomic and transcriptome features for characterization and prognostic prediction of angioimmunoblastic T-cell lymphoma.Annals of hematology · 2025Article
- Clonal Hematopoiesis and Solid Cancers.Cancer science · 2025Review
- Induction of p53-mediated apoptosis by azacitidine in patient-derived xenograft follicular helper T-cell lymphoma model.Leukemia · 2025Article
- TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma.Leukemia · 2025Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Angioimmunoblastic T-cell lymphoma: a concise overview encompassing the pathogenetic, pathological, clinical, therapeutical characteristics, and recent advances.Clinical and experimental medicine · 2025Review
- Discrete genetic subtypes and tumor microenvironment signatures correlate with peripheral T-cell lymphoma outcomes.Leukemia · 2025Article
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Authors and funding
22 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is proposed to be initiated by age-related clonal hematopoiesis (ACH) with TET2 mutations, whereas the G17V RHOA mutation in immature cells with TET2 mutations promotes the development of T follicular helper (TFH)-like tumor cells. Here, we investigated the mechanism by which TET2-mutant immune cells enable AITL development using mouse models and human samples. Among the 2 mouse models, mice lacking Tet2 in all the blood cells (Mx-Cre × Tet2flox/flox × G17V RHOA transgenic mice) spontaneously developed AITL for approximately up to a year, while mice lacking Tet2 only in the T cells (Cd4-Cre × Tet2flox/flox × G17V RHOA transgenic mice) did not. Therefore, Tet2-deficient immune cells function as a niche for AITL development. Single-cell RNA-sequencing (scRNA-seq) of >50 000 cells from mouse and human AITL samples revealed significant expansion of aberrant B cells, exhibiting properties of activating light zone (LZ)-like and proliferative dark zone (DZ)-like germinal center B (GCB) cells. The GCB cells in AITL clonally evolved with recurrent mutations in genes related to core histones. In silico network analysis using scRNA-seq data identified Cd40-Cd40lg as a possible mediator of GCB and tumor cell cluster interactions. Treatment of AITL model mice with anti-Cd40lg inhibitory antibody prolonged survival. The genes expressed in aberrantly expanded GCB cells in murine tumors were also broadly expressed in the B-lineage cells of TET2-mutant human AITL. Therefore, ACH-derived GCB cells could undergo independent clonal evolution and support the tumorigenesis in AITL via the CD40-CD40LG axis.
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