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Grant support

This study was supported by the la Caixa Foundation (CLLEvolution LCF/PR/HR17/52150017; Health Research 2017 Program HR17-00221) (E.C.), the European Research Council under the EU Horizon 2020 research and innovation program BCLLatlas 810287 (E.C.), the Instituto de Salud Carlos III and the European Regional Development Fund Una manera de hacer Europa (project PMP15/00007) (E.C.), the Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR-1142 (E.C.), and CERCA Programme/Generalitat de Catalunya. F.N. is supported by a predoctoral fellowship of the Ministerio de Ciencia e Innovacio ' n (BES2016-076372). E.C. is an academia researcher of the Institucio ' Catalana de Recerca i Estudis Avancats of the Generalitat de Catalunya.

Analysis of institutional authors

Baumann, Tycho StephanAuthorNadeu FCorresponding AuthorClot GAuthorDuran-Ferrer MAuthorNavarro AAuthorMartin SAuthorJares PAuthorMartin-Subero IAuthorDelgado JAuthorCampo ECorresponding Author

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Article

IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics

Publicated to:Blood. 137 (21): 2935-2946 - 2021-05-27 137(21), DOI: 10.1182/blood.2020008311

Authors: Nadeu, Ferran; Royo, Romina; Clot, Guillem; Duran-Ferrer, Marti; Navarro, Alba; Martin, Silvia; Lu, Junyan; Zenz, Thorsten; Baumann, Tycho; Jares, Pedro; Puente, Xose S; Martin-Subero, Jose I; Delgado, Julio; Campo, Elias

Affiliations

Barcelona Supercomp Ctr, Barcelona, Spain - Author
Centro de Investigación Biomédica en Red - Author
Centro Nacional de Supercomputacion - Author
Ctr Invest Biomed Red Canc, Madrid, Spain - Author
European Mol Biol Lab, Heidelberg, Germany - Author
European Molecular Biology Laboratory Heidelberg - Author
Hosp Clin Barcelona, Barcelona, Spain - Author
Hosp Univ 12 Octubre, Dept Hematol, Madrid, Spain - Author
Hospital Clinic Barcelona - Author
Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain - Author
Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain - Author
Institució Catalana de Recerca i Estudis Avançats - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Author
Instituto Universitario de Oncologia del Principado de Asturias - Author
Univ Barcelona, Dept Fonaments Clin, Barcelona, Spain - Author
Univ Hosp, Dept Med Oncol & Hematol, Zurich, Switzerland - Author
Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, Oviedo, Spain - Author
Univ Zurich, Zurich, Switzerland - Author
Universitat de Barcelona - Author
University of Zurich - Author
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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 three CLL subtypes based on methylation signatures reminiscent of naïve-like (n-CLL), intermediate (i-CLL) and memory-like B-cells (m-CLL) with different biological features. i-CLL carry a borderline IGHV mutational load and a significant higher usage of IGHV3-21/IGLV3-21. To determine the clinical and biological features of IGLV3-21R110 CLL and its relationship to these epigenetic subtypes we have characterized the immunoglobulin gene of 584 CLL cases using whole-genome/exome and RNA sequencing. IGLV3-21R110 was detected in 6.5% of cases, being 30/79 (38%) i-CLL, 5/291 (1.7%) m-CLL and 1/189 (0.5%) n-CLL. All stereotype subset #2 cases carried IGLV3-21R110 while 62% of IGLV3-21R110 i-CLL had non-stereotyped B-cell receptor immunoglobulins. IGLV3-21R110 i-CLL had significantly higher number of SF3B1 and ATM mutations, and total number of driver alterations. Nonetheless, the R110 mutation was the sole alteration in one i-CLL and accompanied only by del(13q) in three. Although composite regarding IGHV mutational status, IGLV3-21R110 i-CLL transcriptomically resembled naïve-like/unmutated IGHV CLL with a specific signature including WNT5A/B overexpression. Contrarily, i-CLL lacking the IGLV3-21R110 mirrored memory-like/mutated IGHV cases. IGLV3-21R110 i-CLL had a short time to first treatment and overall survival similar to n-CLL/unmutated IGHV cases whereas non-IGLV3-21R110 i-CLL had a good prognosis similar to memory-like/mutated IGHV. Altogether, IGLV3-21R110 defines a CLL subgroup with specific biological features and an unfavorable prognosis independent of the IGHV mutational status and epigenetic subtypes.Copyright © 2020 American Society of Hematology.

Keywords

cd38 expressionchemotaxisdiseasegenesigmutationsphenotypereceptorssubgroupsAdolescentAdultAgedAged, 80 and overB-lymphocytesDna methylationFemaleGenes, immunoglobulin light chainHumansLeukemia, lymphocytic, chronic, b-cellMaleMiddle agedMutationPoint mutationYoung adult

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Blood due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 2/78, thus managing to position itself as a Q1 (Primer Cuartil), in the category Hematology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 3.94. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 3.61 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 19.34 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-20, the following number of citations:

  • WoS: 58
  • Scopus: 65
  • Europe PMC: 26
  • OpenCitations: 56

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-20:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 72.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 72 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 6.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany; Switzerland.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Nadeu Prat, Ferran) and Last Author (Campo Güerri, Elías).

the authors responsible for correspondence tasks have been Nadeu Prat, Ferran and Campo Güerri, Elías.