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This work was supported by the Instituto Gulbenkian de Ciencia (IGC)-Fundacao Calouste Gulbenkian, by the Portuguese National Research Council (Fundacao para a Ciencia e Tecnologia [FCT], Grant PTDC/BIA-BID/30925/2017) (to V.C.M.). R.A.P. is a Ph.D. student of the IGC Integrative Biology and Biomedicine Ph.D. Program and is supported by an individual Ph.D. fellowship from the FCT (PD/BD/114341/2016). This work was developed with the support of the research infrastructure Congento, Project Grant LISBOA-01-0145-FEDER-022170, and ONEIDA project Grant LISBOA-01-0145-FEDER-016417, both cofinanced by Lisboa Regional Operational Programme (Lisboa 2020) under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund and FCT.

Analysis of institutional authors

Ballesteros-Arias, LunaAuthor

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May 30, 2022
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T Cell Acute Lymphoblastic Leukemia as a Consequence of Thymus Autonomy

Publicated to:Journal Of Immunology. 202 (4): 1137-1144 - 2019-02-15 202(4), DOI: 10.4049/jimmunol.1801373

Authors: Ballesteros-Arias, Luna; Silva, Joana G; Paiva, Rafael A; Carbonetto, Belen; Faisca, Pedro; Martins, Vera C

Affiliations

Fundacao Calouste Gulbenkian, Inst Gulbenkian Ciencia, Bioinformat Unit, P-2780156 Oeiras, Portugal - Author
Fundacao Calouste Gulbenkian, Inst Gulbenkian Ciencia, Histopathol Unit, P-2780156 Oeiras, Portugal - Author
Fundacao Calouste Gulbenkian, Inst Gulbenkian Ciencia, Lymphocyte Dev & Leukemogenesis Lab, P-2780156 Oeiras, Portugal - Author

Abstract

Thymus autonomy is the capacity of the thymus to maintain T lymphocyte development and export independently of bone marrow contribution. Prolonging thymus autonomy was shown to be permissive to the development of T cell acute lymphoblastic leukemia (T-ALL), similar to the human disease. In this study, performing thymus transplantation experiments in mice, we report that thymus autonomy can occur in several experimental conditions, and all are permissive to T-ALL. We show that wild type thymi maintain their function of T lymphocyte production upon transplantation into recipients with several genotypes (and corresponding phenotypic differences), i.e., Rag2(-/-) gamma(-/-)(c), gamma(-/-)(c), Rag2(-/-) IL-7r alpha(-/-), and IL-7r alpha(-/-). We found that the cellularity of the thymus grafts is influenced exclusively by the genotype of the host, i.e., IL-7r alpha(-/-) versus gamma(-/-)(c) Nonetheless, the difference in cellularity detected in thymus autonomy bore no impact on onset, incidence, immunophenotype, or pathologic condition of T-ALL. In all tested conditions, T-ALL reached an incidence of 80%, demonstrating that thymus autonomy bears a high risk of leukemia. We also analyzed the microbiota composition of the recipients and their genetic background, but none of the differences found influenced the development of T-ALL. Taken together, our data support that IL-7 drives cellular turnover non-cell autonomously, which is required for prevention of T-ALL. We found no influence for T-ALL in the specific combination of the genotypic mutations tested (including the developmental block caused by Rag deficiency), in microbiota composition, or minor differences in the genetic background of the strains.

Keywords

AbsenceAnimalsExpressionGene-therapyInterleukin-7 receptor, alpha chainLymphoid developmentMiceMice, inbred c57blMice, knockoutMutationsPrecursor t-cell lymphoblastic leukemia-lymphomaReceptors, interleukin-7Self-renewalSevere combined immunodeficiencyThymocytesThymus gland

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Immunology due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

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: 3.78, 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 Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-09, the following number of citations:

  • WoS: 15
  • Scopus: 14
  • Europe PMC: 9

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 2025-07-09:

  • 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: 33.
  • 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: 34 (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: 96.23.
  • The number of mentions on the social network X (formerly Twitter): 16 (Altmetric).
  • The number of mentions in news outlets: 11 (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: Portugal.

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 (Ballesteros Arias, Luna Laura) .