2026-07-23T20:35:14Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/189252024-11-29T13:26:11Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2023-08-08 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. Blood Adv . 2023 ;7(15):4135-4147. 10.1182/bloodadvances.2021006336 2473-9537 Blood advances 36459489 http://hdl.handle.net/20.500.12105/18925 JAK/STAT blockade reverses the malignant phenotype of Hodgkin and Reed-Sternberg cells.