Observational studyLeukemia2021
Targeted deep sequencing reveals clonal and subclonal mutational signatures in Adult T-cell leukemia/lymphoma and defines an unfavorable indolent subtype.
Observational study in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Trial
- HTLV-1 HBZ inhibits DHX9 to reprogram circRNA biogenesis in ATLL.Tumour virus research · 2026Article
- From Genomic and Epigenomic Maps to Medicines in Adult T-Cell Leukemia/Lymphoma.Cancer science · 2026Review
- Perspectives on the origin and therapeutic opportunities in Down syndrome-associated leukemia.Cancer metastasis reviews · 2025Review
- Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations.Haematologica · 2024Article
- A practical approach to the modern diagnosis and classification of T- and NK-cell lymphomas.Blood · 2024Review
- Article
- Gene-to-gene coordinated regulation of transcription and alternative splicing by 3D chromatin remodeling upon NF-κB activation.Nucleic acids research · 2024Article
- Follicular helper T-cell lymphomas: disease spectrum, relationship with clonal hematopoiesis, and mimics. A report of the 2022 EA4HP/SH lymphoma workshop.Virchows Archiv : an international journal of pathology · 2023Review
- Mature T-cell and NK-cell lymphomas: updates on molecular genetic features.International journal of hematology · 2023Review
- How molecular advances may improve the diagnosis and management of PTCL patients.Frontiers in oncology · 2023Review
- Regulation of human T-cell leukemia virus type 1 antisense promoter by myocyte enhancer factor-2C in the context of adult T-cell leukemia and lymphoma.Haematologica · 2022Article
- Article
- RAISING is a high-performance method for identifying random transgene integration sites.Communications biology · 2022Article
- Genetic Alterations in Adult T-Cell Leukemia/Lymphoma: Novel Discoveries with Clinical and Biological Significance.Cancers · 2022Review
- Clonal Selection and Evolution of HTLV-1-Infected Cells Driven by Genetic and Epigenetic Alteration.Viruses · 2022Review
- Genetic profiling and biomarkers in peripheral T-cell lymphomas: current role in the diagnostic work-up.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Review
- The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.PLoS pathogens · 2021Article
- Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma.Nature communications · 2021Article
- Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.Molecular cancer · 2021Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adult T-cell leukemia/lymphoma (ATL) carries a poor prognosis even in indolent subtypes. We performed targeted deep sequencing combined with mapping of HTLV-1 proviral integration sites of 61 ATL patients of African and Caribbean origin. This revealed mutations mainly affecting TCR/NF-kB (74%), T-cell trafficking (46%), immune escape (29%), and cell cycle (26%) related pathways, consistent with the genomic landscape previously reported in a large Japanese cohort. To examine the evolution of mutational signatures upon disease progression while tracking the viral integration architecture of the malignant clone, we carried out a longitudinal study of patients who either relapsed or progressed from an indolent to an aggressive subtype. Serial analysis of relapsing patients identified several patterns of clonal evolution. In progressing patients, the longitudinal study revealed NF-kB/NFAT mutations at progression that were present at a subclonal level at diagnosis (allelic frequency < 5%). Moreover, the presence in indolent subtypes of mutations affecting the TCR/NF-kB pathway, whether clonal or subclonal, was associated with significantly shorter time to progression and overall survival. Our observations reveal the clonal dynamics of ATL mutational signatures at relapse and during progression. Our study defines a new subgroup of indolent ATLs characterized by a mutational signature at high risk of transformation.
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Registered trials
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 Socratic graph.