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December 8, 2025Blood

Targets of BTK and IRAK4 pathways in cns lymphoma: Identification of CXCL10 as a prognostic biomarker in CSF and its receptor, CXCR3, as a mediator of pro-survival signaling

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Authors

MLMing‐Chi LuASAbu Jafar Mohammed SalehJRJames L. Rubenstein

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Overview

Transcriptional profiling reveals CXCL10 as a key chemokine in CNS lymphoma, suggesting its role alongside CXCR3 in survival mechanisms.

Key Points

  • To identify targets of the BTK and IRAK4 pathways in CNS lymphoma and assess CXCL10 and its receptor CXCR3 as prognostic biomarkers.
  • Conducted transcriptional profiling via RNA-Seq of patient-derived CNS lymphoma cells post-treatment with AZ1495 and ibrutinib.
  • Measured CXCL10 levels in cerebrospinal fluid from PCNSL patients and compared with non-malignant controls.
  • Evaluated in vitro survival impacts of CXCL10 and CXCR3 expression in MYD88 mutant lymphoma models.
  • CXCL10 levels in CSF at diagnosis were higher in PCNSL patients, correlating with shorter overall survival.
  • CXCR3 expression was significantly increased with combination therapy, indicating a pro-survival role.
  • Reduction of CXCL10 or CXCR3 expression led to >50% decrease in lymphoma cell survival under low serum conditions.

Cite This Study

Lu et al. (2025) studied this question.

synapsesocial.com/papers/69362f5a4fa91c937236db12https://doi.org/10.1182/blood-2025-5321
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