ArticleBlood2021
IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- A genetic profiling guideline to support diagnosis and clinical management of lymphomas.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Guideline
- IGLV3-21HemaSphere · 2026Article
- Advancing Immunotherapy in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2026Review
- Outcomes of patients with CLL and borderline IGHV mutational status: a systematic review and meta analysis.Biomarker research · 2026Article
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- Molecular Pathogenesis and Targeted Treatment of Richter Transformation.Biomedicines · 2026Review
- Molecular and functional characterization of the B-cell receptor in chronic lymphocytic leukemia-like monoclonal B-cell lymphocytosis.Leukemia · 2026Article
- IGLV3-21Haematologica · 2026Article
- Identification of two epitypes of IGHV unmutated chronic lymphocytic leukemia with distinct B-cell-related epigenetic imprinting and genetic alterations.HemaSphere · 2026Article
- Epigenetics in B-CLL.International journal of genomics · 2026Review
- The Chronic Lymphocytic Leukemia Epigenome: A Powerful and Stable Framework for Understanding Biological and Clinical Heterogeneity.Hematology/oncology clinics of North America · 2025Review
- Article
- Molecular Features Accompanying Richter's Transformation in Patients with Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2025Review
- Targeted therapies overcome the poor prognosis of stereotyped Subset#2 chronic lymphocytic leukemia : a real-world multicentric study.Leukemia · 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
- Article
- High-throughput Sequencing Reveals that BCR and TCR Repertoires as Potential Prognostic Biomarkers for Pediatric Patients with B-ALL.Current genomics · 2025Article
- Stereotyped B-Cell Receptor Immunoglobulins in B-Cell Lymphomas.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies.Biomarker research · 2024Review
- Article
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B-cell receptor (BCR) signaling is crucial for chronic lymphocytic leukemia (CLL) biology. IGLV3-21-expressing B cells may acquire a single point mutation (R110) that triggers autonomous BCR signaling, conferring aggressive behavior. Epigenetic studies have defined 3 CLL subtypes based on methylation signatures reminiscent of naïve-like (n-CLL), intermediate (i-CLL), and memory-like (m-CLL) B cells with different biological features. i-CLL carries a borderline IGHV mutational load and significantly higher use of IGHV3-21/IGLV3-21. To determine the clinical and biological features of IGLV3-21R110 CLL and its relationship to these epigenetic subtypes, we characterized the immunoglobulin gene of 584 CLL cases using whole-genome/exome and RNA sequencing. IGLV3-21R110 was detected in 6.5% of cases: 30 (38%) of 79 i-CLLs, 5 (1.7%) of 291 m-CLLs, and 1 (0.5%) of 189 n-CLLs. All stereotype subset 2 cases carried IGLV3-21R110, whereas 62% of IGLV3-21R110 i-CLL cases had nonstereotyped BCR immunoglobulins. IGLV3-21R110 i-CLL had a significantly higher number of SF3B1 and ATM mutations and total number of driver alterations. However, the R110 mutation was the sole alteration in 1 i-CLL and was accompanied only by del(13q) in 3. Although IGHV mutational status varied, IGLV3-21R110 i-CLL transcriptomically resembled n-CLL/unmutated IGHV CLL with a specific signature including WNT5A/B overexpression. In contrast, i-CLL lacking IGLV3-21R110 mirrored m-CLL/mutated IGHV. Patients with IGLV3-21R110 i-CLL had a short time to first treatment and overall survival similar to those of n-CLL/unmutated IGHV patients, whereas patients with non-IGLV3-21R110 i-CLL had a good prognosis similar to that of patients with m-CLL/mutated IGHV. IGLV3-21R110 defines a CLL subgroup with specific biological features and an unfavorable prognosis independent of IGHV mutational status and epigenetic subtype.
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