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Analysis of institutional authors

Gimenez NAuthorGiro, AAuthorRosich, LAuthorLopez-Guerra, MAuthorLópez-Oreja IAuthorPlayà-Albinyana HAuthorArenas, FAuthorPerez-Galan, PAuthorDelgado, JAuthorCampo, EAuthorColomer, DCorresponding Author

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February 12, 2021
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Article

Systems biology drug screening identifies statins as enhancers of current therapies in chronic lymphocytic leukemia

Publicated to:Scientific Reports. 10 (1): 22153- - 2020-12-17 10(1), DOI: 10.1038/s41598-020-78315-0

Authors: Gimenez, Neus; Tripathi, Rupal; Giro, Ariadna; Rosich, Laia; Lopez-Guerra, Monica; Lopez-Oreja, Irene; Playa-Albinyana, Heribert; Arenas, Fabian; Mas, Jose Manuel; Perez-Galan, Patricia; Delgado, Julio; Campo, Elias; Farres, Judith; Colomer, Dolors

Affiliations

Anax Biotech, Barcelona, Spain - Author
Anaxomics Biotech - Author
Anaxomics Biotech, Barcelona, Spain. - Author
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain - Author
Barcelona Institute of Science and Technology (BIST) - Author
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain. - Author
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain. - Author
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain. dcolomer@clinic.cat. - Author
Centros de Investigacion Biomedica en Red (CIBER) - Author
Ctr Invest Biomed Red Canc CIBERONC, Barcelona, Spain - Author
Department of Hematology, Hospital Clinic, IDIBAPS, Barcelona, Spain. - Author
Experimental Therapeutics in Lymphoid Malignancies Group, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. - Author
Experimental Therapeutics in Lymphoid Malignancies Group, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. dcolomer@clinic.cat. - Author
Hematopathology Unit, Department of Pathology, Hospital Clinic, IDIBAPS, Barcelona, Spain. - Author
Hematopathology Unit, Department of Pathology, Hospital Clinic, IDIBAPS, Barcelona, Spain. dcolomer@clinic.cat. - Author
Hosp Clin Barcelona, Dept Hematol, IDIBAPS, Barcelona, Spain - Author
Hosp Clin Barcelona, Dept Pathol, Hematopathol Unit, IDIBAPS, Barcelona, Spain - Author
Hospital Clinic Barcelona - Author
IDIBAPS, Microenvironm Lymphoma Pathogenesis & Therapy Grp, Barcelona, Spain - Author
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Expt Therapeut Lymphoid Malignancies Grp, Barcelona, Spain - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Author
Microenvironment in Lymphoma Pathogenesis and Therapy Group, IDIBAPS, Barcelona, Spain. - Author
Univ Barcelona, Barcelona, Spain - Author
Universitat de Barcelona - Author
University of Barcelona, Barcelona, Spain. - Author
University of Barcelona, Barcelona, Spain. dcolomer@clinic.cat. - Author
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Abstract

Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. We used a platform for drug discovery based on systems biology and artificial intelligence, to identify drugs targeting key proteins described to have a role in the microenvironment. The selected compounds were screened in CLL cell lines in the presence of stromal cells to mimic the microenvironment and validated the best candidates in primary CLL cells. Our results showed that the commercial drug simvastatin was the most effective and selective out of the tested compounds. Simvastatin decreased CLL cell survival and proliferation as well as cell adhesion. Importantly, this drug enhanced the antitumor effect of venetoclax and ibrutinib. We proposed that systems biology approaches combined with pharmacological screening could help to find new drugs for CLL treatment and to predict new combinations with current therapies. Our results highlight the possibility of repurposing widely used drugs such as statins to target the microenvironment and to improve the efficacy of ibrutinib or venetoclax in CLL cells.

Keywords

Antineoplastic agentsBiomarkersCell proliferationCell survivalDrug evaluation, preclinicalDrug screening assays, antitumorDrug synergismGene expression regulation, leukemicHumansHydroxymethylglutaryl-coa reductase inhibitorsLeukemia, lymphocytic, chronic, b-cellModels, molecularReproducibility of resultsSignal transductionSmall molecule librariesStructure-activity relationshipSystems biologyTumor microenvironment

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Scientific Reports 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, 2020, it was in position 17/72, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.99, which 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: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-21, the following number of citations:

  • WoS: 17
  • Scopus: 19
  • Europe PMC: 16

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 2025-08-21:

  • 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: 60.
  • 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: 60 (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: 0.75.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Mali.

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 (Gimenez Gracia, Nuria) and Last Author (Colomer Pujol, Dolors).

the author responsible for correspondence tasks has been Colomer Pujol, Dolors.