ArticleBlood advances2022
Clonotype pattern in T-cell lymphomas map the cell of origin to immature lymphoid precursors.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
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- Analysis of Hyperexpanded T Cell Clones in SARS-CoV-2 Vaccine-Associated Liver Injury by Spatial Proteomics and Transcriptomics.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Molecular Insights into the Diagnosis of Anaplastic Large Cell Lymphoma: Beyond Morphology and Immunophenotype.International journal of molecular sciences · 2025Review
- Generative artificial intelligence, integrative bioinformatics, and single-cell analysis reveal Alzheimer's genetic and immune landscape.Molecular therapy. Nucleic acids · 2025Article
- Sex-specific differences in reproductive tract lymphomas: epidemiology, clinical features, and treatment outcomes.The oncologist · 2025Article
- T-cell receptor architecture and clonal tiding provide insight into the transformation trajectory of peripheral T-cell lymphomas.Haematologica · 2025Article
- Reply to: Oligoclonality of TRBC1 and TRBC2 in T cell lymphomas as mechanism of primary resistance to TRBC-directed CAR T cell therapies.Nature communications · 2025Article
- Oligoclonality of TRBC1 and TRBC2 in T cell lymphomas as mechanism of primary resistance to TRBC-directed CAR T cell therapies.Nature communications · 2025Article
- T cell receptor-centric perspective to multimodal single-cell data analysis.Science advances · 2024Article
- Multi-Omic Data Integration Suggests Putative Microbial Drivers of Aetiopathogenesis in Mycosis Fungoides.Cancers · 2024Article
- T cell receptor-directed antibody-drug conjugates for the treatment of T cell-derived cancers.Molecular therapy. Oncology · 2024Article
- Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies.Nature communications · 2024Article
- Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy.Nature communications · 2024Article
- Sézary syndrome originates from heavily mutated hematopoietic progenitors.Blood advances · 2023Article
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mature T-cell lymphomas (TCLs) are rare, clinically heterogeneous hematologic cancers with high medical need. TCLs have an inferior prognosis which is attributed to poor understanding of their pathogenesis. On the basis of phenotypic similarities between normal and neoplastic lymphocytes, it has been assumed that TCLs develop in the periphery, directly from various subtypes of normal T cells. To address the debated question of the cell of origin in TCLs, we attempted to identify the highly variable complementarity-determining regions (CDRs) of T-cell receptors (TCRs) to trace the clonal history of the T cells. We have collected previously published whole-genome, whole-exome, and whole-transcriptome sequencing data from 574 patients with TCL. TCR clonotypes were identified by de novo assembly of CDR3 regions of TCRα, TCRβ, and TCRγ. We have found that the vast majority of TCLs are clonotypically oligoclonal, although the pattern of oligoclonality varied. Anaplastic large-cell lymphoma was the most diverse comprising multiple clonotypes of TCRα, TCRβ, and TCRγ, whereas adult TCL or leukemia and peripheral TCLs often showed monoclonality for TCRβ and TCRγ but had diverse TCRα clonotypes. These patterns of rearrangements indicated that TCLs are initiated at the level of the lymphoid precursor. In keeping with this hypothesis, TCR rearrangements in TCLs resembled the pattern seen in the human thymus, which showed biased usage of V (variable) and J (joining) segments of high combinatorial probability resulting in recurrent public CDR3 sequences shared across unrelated patients and different clinical TCL entities. Clonotypically diverse initiating cells may seed target tissues that are then responsible for disease relapses after therapy.
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