Evidence map›Paper›PMID 40489893›Full record

ArticleBlood advances2025

Thyroid hormones contribute to JAK/STAT pathway abnormal activation, promoting T-cell lymphoma dissemination.

Mercedes Debernardi, Alejandro Correa, Lucero Alvarado, María Victoria Revuelta, Helena Andrea Sterle, Gonzalo Gonzalez, Ingrid Larissa Melo Souza, Jorgelina Real, María Teresa Garcia de Dávila, Johanna Abigail Díaz Albuja and 4 more

Abstract read
In one paragraph

Article in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Mercedes DebernardiLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0000-0002-1355-362X
Alejandro CorreaLaboratory of Basic Biology of Stem Cells, Carlos Chagas Institute, Oswaldo Cruz Foundation, Curitiba, Brazil.ORCID 0000-0002-5887-1453
Lucero AlvaradoLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0009-0006-7419-7813
María Victoria RevueltaHematology and Oncology Division, Department of Medicine, Weill Cornell Medicine, New York, NY.ORCID 0000-0002-7922-0713
Helena Andrea SterleLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0000-0002-6889-6398
Gonzalo GonzalezLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0009-0007-3602-7116
Ingrid Larissa Melo SouzaLaboratory of Basic Biology of Stem Cells, Carlos Chagas Institute, Oswaldo Cruz Foundation, Curitiba, Brazil.ORCID 0000-0002-1151-5021
Jorgelina RealPathology Department, British Hospital, Buenos Aires, Argentina.
María Teresa Garcia de DávilaPathology Department, British Hospital, Buenos Aires, Argentina.ORCID 0000-0002-3561-5035
Johanna Abigail Díaz AlbujaLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0009-0000-7222-0879
Cinthia RosemblitLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0000-0002-7956-6829
Leandro CerchiettiHematology and Oncology Division, Department of Medicine, Weill Cornell Medicine, New York, NY.ORCID 0000-0003-0608-1350
Graciela Alicia CremaschiLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0000-0002-1131-1723
Florencia CayrolLaboratory of Neuroimmunomodulation and Molecular Oncology, Instituto de Investigaciones Biomédicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Catolica Argentina, Buenos Aires, Argentina.ORCID 0000-0002-9622-4150

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractAbnormal JAK/STAT pathway activation is widespread in virtually all T-cell lymphoma (TCL) subtypes. However, activating mutations are insufficient to drive leukemic cell proliferation, which also requires enhanced upstream signaling. We have described that thyroid hormones (THs) contribute to the malignant phenotype of TCL by inducing intracellular transcriptional programs through integrin αvβ3 activation. Here, we evaluate the effect of THs on the JAK/STAT pathway and its implications on TCL therapy. We found that THs induce the activation of STAT1, 3, and 5, including the upregulation of target genes and metalloprotease activity. Furthermore, we observed that the integrin αvβ3 inhibitor, cilengitide, not only reverts these effects but also enhances the antilymphoma activity to a greater extent than the JAK1/2 inhibitor, ruxolitinib, when combined with bexarotene, a synthetic rexinoid clinically used for cutaneous TCL treatment. Furthermore, we explored the mechanisms of action of cilengitide and bexarotene combination using preclinical TCL in vivo models and proteomic analysis. We found that this combinatorial protocol significantly reduced tumor STATs phosphorylation, matrix metalloproteinase activity, and the number of metastatic foci by regulating proteins involved in cell proliferation, angiogenesis, metabolism, and immune response. In addition, we observed that high integrin αvβ3 messenger RNA levels are enriched in pathways associated with lymphoma progression and reduce overall survival in samples from patients with TCL. Our findings support the therapeutic potential of targeting THs signaling through integrin αvβ3 inhibition in combination with bexarotene as a less toxic therapeutic strategy to mitigate aberrant JAK/STAT activation and limit lymphoma dissemination.

Indexed as

Janus KinasesLymphoma, T-CellSignal TransductionSTAT Transcription FactorsThyroid HormonesAnimalsCell Line, TumorHumansMiceJanus KinasesSTAT Transcription FactorsThyroid Hormones

Identifiers

PMID40489893
PMCPMC12372972

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