2026-07-23T20:34:42Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/189252024-11-29T13:26:11Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Fernández, Sara
author
Solórzano, Jose L
author
Díaz, Eva
author
Menéndez, Victoria
author
Maestre, Maestre L
author
Palacios, Sara
author
López, Mar
author
Colmenero, Argentina
author
Estévez, Mónica
author
Montalbán, Carlos
author
Martínez, Ángel
author
Roncador, Giovanna
author
García, Juan F
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Roche
2024-03-13T11:56:57Z
2024-03-13T11:56:57Z
2023-08-08
Blood Adv . 2023 ;7(15):4135-4147.
10.1182/bloodadvances.2021006336
2473-9537
Blood advances
36459489
http://hdl.handle.net/20.500.12105/18925
Constitutive activation of the JAK/STAT pathway is a common phenomenon in classic Hodgkin lymphoma (cHL). The clinical potential of anti-JAK/STAT therapy is being explored in early-stage clinical trials. Notwithstanding, very little information is available about the complex biological consequences of this blockade. Here, we investigated the effects of JAK/STAT pharmacological inhibition on cHL cell models using ruxolitinib, a JAK 1/2 inhibitor that induces apoptosis by concentration- and time-dependent mechanisms. An unbiased whole-transcriptome approach identified expression of the anti-GCSF receptor (CSF3R) as a potential surrogate biomarker of JAK/STAT overactivation. In addition, longitudinal gene expression analyses provided further mechanistic information about pertinent biological pathways involved, including 37 gene pathways distributed in 3 main clusters: cluster 1 was characterized by upregulation of the G2/M checkpoint and major histocompatibility complex-related clusters; 2 additional clusters (2 and 3) showed a progressive downregulation of the tumor-promoting inflammation signatures: JAK/STAT and interleukin 1 (IL-1)/IL-4/IL-13/IL-17. Together, our results confirm the therapeutic potential of JAK/STAT inhibitors in cHL, identify CSF3R as a new biomarker, and provide supporting genetic data and mechanistic understanding.
eng
JAK/STAT blockade reverses the malignant phenotype of Hodgkin and Reed-Sternberg cells.
journal article
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https://repisalud.isciii.es/bitstreams/e074408b-d00c-4c9c-8ff9-f5e350252e33/download
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JAKSTATblockadereversesthemalignant_2022.pdf
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https://repisalud.isciii.es/bitstreams/059a848a-8a24-425b-8d25-682b76e7d839/download
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text/plain
JAKSTATblockadereversesthemalignant_2022.pdf.txt