ArticleLeukemia2017
Targeted deep sequencing reveals clinically relevant subclonal IgHV rearrangements in chronic lymphocytic leukemia.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis.The Cochrane database of systematic reviews · 2020Pooled it
- Stereotyped CLL-like immunoglobulin rearrangements in healthy repertoires: implications for leukemogenesis.Frontiers in immunology · 2026Review
- [High-throughput sequencing in identifying somatic hypermutation in immunoglobulin heavy chain variable regions with complex clonal backgrounds].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Chronic lymphocytic leukemia often arises by a multiclonal selection process.Haematologica · 2025Article
- [Application of next-generation sequencing technology for the investigation of immunoglobulin variable region characteristics and their prognostic significance in patients with chronic lymphocytic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Recent Advances in the Molecular Biology of Chronic Lymphocytic Leukemia: How to Define Prognosis and Guide Treatment.Cancers · 2024Review
- Review
- Clonal Characterization and Somatic Hypermutation Assessment by Next-Generation Sequencing in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Detailed Description of the Technical Performance, Clinical Utility, and Platform Comparison.The Journal of molecular diagnostics : JMD · 2023Article
- A novel next-generation sequencing capture-based strategy to report somatic hypermutation status using genomic regions downstream to immunoglobulin rearrangements.Haematologica · 2023Article
- B cell M-CLL clones retain selection against replacement mutations in their immunoglobulin gene framework regions.Frontiers in oncology · 2023Article
- Clonally unrelated Richter syndrome are truly de novo diffuse large B-cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome.British journal of haematology · 2022Article
- Review
- Panel Sequencing for Clinically Oriented Variant Screening and Copy Number Detection in Chronic Lymphocytic Leukemia Patients.Diagnostics (Basel, Switzerland) · 2022Article
- Evidence of somatic hypermutation in the antigen binding sites of patients with CLL harboring IGHV genes with 100% germline identity.Frontiers in oncology · 2022Article
- Characterization of Chronic Lymphocytic Leukemia Immunoglobulin Rearrangements from Partial Read Sequencing.Genomics, proteomics & bioinformatics · 2022Article
- Nanopore sequencing approach for immunoglobulin gene analysis in chronic lymphocytic leukemia.Scientific reports · 2021Article
- Immune Gene Rearrangements: Unique Signatures for Tracing Physiological Lymphocytes and Leukemic Cells.Genes · 2021Review
- Clonal dynamics in a composite chronic lymphocytic leukemia and hairy cell leukemia-variant.Genes, chromosomes & cancer · 2021Article
- CRIS: complete reconstruction of immunoglobulinBioinformatics advances · 2021Article
- Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunoglobulin heavy-chain variable region gene (IgHV) mutational status is considered the gold standard of prognostication in chronic lymphocytic leukemia (CLL) and is currently determined by Sanger sequencing that allows the analysis of the major clone. Using next-generation sequencing (NGS), we sequenced the IgHV gene from two independent cohorts: (A) 270 consecutive patient samples obtained at diagnosis and (B) 227 patients from the UK ARCTIC-AdMIRe clinical trials. Using complementary DNA from purified CD19+CD5+ cells, we demonstrate the presence of multiple rearrangements in independent experiments and showed that 24.4% of CLL patients express multiple productive clonally unrelated IgHV rearrangements. On the basis of IgHV-NGS subclonal profiles, we defined five different categories: patients with (a) multiple hypermutated (M) clones, (b) 1 M clone, (c) a mix of M-unmutated (UM) clones, (d) 1 UM clone and (e) multiple UM clones. In population A, IgHV-NGS classification stratified patients into five different subgroups with median treatment-free survival (TFS) of >280(a), 131(b), 94(c), 29(d), 15(e) months (P<0.0001) and a median OS of >397(a), 292(b), 196(c), 137(d) and 100(e) months (P<0.0001). In population B, the poor prognosis of multiple UM patients was confirmed with a median TFS of 2 months (P=0.0038). In conclusion, IgHV-NGS highlighted one quarter of CLL patients with multiple productive IgHV subclones and improves disease stratification and raises important questions concerning the pre-leukemic cellular origin of CLL.
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