{rfName}
Th

Indexed in

License and use

Citations

121

Altmetrics

Grant support

We thank J.C. Aster, C. Cabanas, A. Ferrando, M. Mellado, M.L. Gaspar, B. Andres, A. Ursa and D.J.J. Waugh for providing useful reagents; M. A. Marcos for mouse transplantation advice; B. Alarcon, J.L. de la Pompa J. Fernandez-Piqueras, S. Rodriguez de Cordoba, M. Ramirez and C. Lopez-Larrea for helpful discussions and advice; Centro de Transfusion de la Comunidad de Madrid and the Pediatric Cardiosurgery Units from Ciudad Sanitaria La Paz (Madrid, Spain) for CB and thymus samples, respectively; and the Genomics and New Generation Sequencing Facility at the CBMSO for landscape chromatin analysis. This work was supported by funds from the Ministerio de Economia y Competitividad (MINECO) PLE-2009-0110, SAF2010-15106, SAF2013-44857-R, and SAF2016-75442-R (Agencia Estatal de Investigacion/European Regional Development Fund, European Union), the Fundacion Sandra Ibarra, the Fundacion Asociacion Espanola Contra el Cancer (AECC CI13131229), the Instituto de Salud Carlos III (RTICC RD06/0014/1012), and the European Union Seventh Framework Programme (FP7/2007-20013) ThymiStem project (602587). Institutional grants from the Fundacion Ramon Areces and Banco de Santander to the CBMSO are also acknowledged. MM and MJGL were supported by MINECO.

Analysis of institutional authors

Fuentes, PatriciaAuthorRodriguez, AntonioAuthorMunoz-Calleja, CeciliaAuthorSanchez-Madrid, FranciscoAuthor

Share

July 23, 2018
Publications
>
Article
Bronze

The NOTCH1/CD44 axis drives pathogenesis in a T cell acute lymphoblastic leukemia model

Publicated to:JOURNAL OF CLINICAL INVESTIGATION. 128 (7): 2802-2818 - 2018-07-02 128(7), DOI: 10.1172/JCI92981

Authors: Garcia-Peydro, Marina; Fuentes, Patricia; Mosquera, Marta; Garcia-Leon, Maria J; Alcain, Juan; Rodriguez, Antonio; Garcia de Miguel, Purificacion; Menendez, Pablo; Weijer, Kees; Spits, Hergen; Scadden, David T; Cuesta-Mateos, Carlos; Munoz-Calleja, Cecilia; Sanchez-Madrid, Francisco; Toribio, Maria L

Affiliations

Fdn Ctr Nacl Invest Cardiovasc Carlos III, Dept Vasc Biol & Inflammat, Madrid, Spain - Author
Harvard Stem Cell Inst, Boston, MA USA - Author
Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Med Sch, Boston, MA 02115 USA - Author
Hosp Univ La Paz, Hematooncol & Pediat Bone Marrow Transplantat Uni, Madrid, Spain - Author
ICREA, Barcelona, Spain - Author
ISCIII, Ctr Invest Biomed Red Canc CIBER ONC, Barcelona, Spain - Author
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA - Author
UAM, Hosp Univ Princesa, Serv Inmunol, IIS IP, Madrid, Spain - Author
Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Amsterdam, Netherlands - Author
Univ Amsterdam, Acad Med Ctr, Tytgat Inst Liver & Intestinal Res, Amsterdam, Netherlands - Author
Univ Autonoma Madrid, CSIC UAM, Ctr Biol Mol Severo Ochoa, Dept Cell Biol & Immunol, Madrid, Spain - Author
Univ Autonoma Madrid, Dept Mol Biol, Madrid, Spain - Author
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Barcelona, Spain - Author
Univ Barcelona, Sch Med, Dept Biomed, Barcelona, Spain - Author
See more

Abstract

NOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1. This T-ALL model allowed us to identify CD44 as a direct NOTCH1 transcriptional target and to recognize CD44 overexpression as an early hallmark of preleukemic cells that engraft the BM and finally develop a clonal transplantable T-ALL that infiltrates lymphoid organs and brain. Notably, CD44 is shown to support crucial BM niche interactions necessary for LIC activity of human T-ALL xenografts and disease progression, highlighting the importance of the NOTCH1/CD44 axis in T-ALL pathogenesis. The observed therapeutic benefit of anti-CD44 antibody administration in xenotransplanted mice holds great promise for therapeutic purposes against T-ALL relapse.

Keywords

bone marrowhematologyleukemiasoncologyBone-marrowBreast-cancer cellsC-mycCd44Dynamic interactionsEssential rolesGamma-secretase inhibitorsGene-expressionNotchStem-cellsT cell development

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF CLINICAL INVESTIGATION 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, 2018, it was in position 3/135, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, Research & Experimental. 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: 1.91. 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: 2.76 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 8.36 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-18, the following number of citations:

  • WoS: 40
  • Scopus: 45
  • Europe PMC: 32

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 2025-07-18:

  • 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: 70.85.
  • The number of mentions on the social network Facebook: 3 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 6 (Altmetric).
  • The number of mentions in news outlets: 7 (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: Netherlands; United States of America.

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 (Garcia-Peydro, Marina) and Last Author (Toribio, Maria L.).