JAK/STAT blockade reverses the malignant phenotype of Hodgkin and Reed-Sternberg cells.

Autor:	Fernández S; Translational Research Laboratory, MD Anderson Cancer Center Madrid, Madrid, Spain., Solórzano JL; Department of Pathology, MD Anderson Cancer Center Madrid, Madrid, Spain., Díaz E; Translational Research Laboratory, MD Anderson Cancer Center Madrid, Madrid, Spain., Menéndez V; Translational Research Laboratory, MD Anderson Cancer Center Madrid, Madrid, Spain., Maestre L; Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Palacios S; Translational Research Laboratory, MD Anderson Cancer Center Madrid, Madrid, Spain., López M; Translational Research Laboratory, MD Anderson Cancer Center Madrid, Madrid, Spain., Colmenero A; Flow Cytometry Unit, Eurofins-Megalab, MD Anderson Cancer Center Madrid, Madrid, Spain., Estévez M; Department of Hematology, MD Anderson Cancer Center Madrid, Madrid, Spain., Montalbán C; Department of Hematology, MD Anderson Cancer Center Madrid, Madrid, Spain., Martínez Á; Cytogenetic Unit, Eurofins-Megalab, MD Anderson Cancer Center Madrid, Madrid, Spain., Roncador G; Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., García JF; Translational Research Laboratory, MD Anderson Cancer Center Madrid, Madrid, Spain.; Department of Pathology, MD Anderson Cancer Center Madrid, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Aug 08; Vol. 7 (15), pp. 4135-4147.
DOI:	10.1182/bloodadvances.2021006336
Abstrakt:	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. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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