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December 8, 2025Blood

The effects of bruton tyrosine kinase inhibitors on the waldenstrom macroglobulinemia microenvironment

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Authors

SBStephen BlackmoreSESherine F. Elsawa

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Overview

Inhibition of BTK alters chemokines and macrophage recruitment in waldenstrom macroglobulinemia, suggesting immune modulation effects.

Key Points

  • To explore how Bruton's tyrosine kinase (BTK) inhibitors affect the immune microenvironment in Waldenstrom macroglobulinemia (WM).
  • Investigated the impact of BTK inhibitors on transcriptional landscape in WM models using RNA-seq
  • Analyzed changes in cytokine and chemokine gene expressions after treatment with acalabrutinib and ibrutinib
  • Assessed macrophage migration in response to conditioned media from treated WM cells
  • Co-cultured WM cells with M0 macrophages to evaluate tumor-immune interactions
  • Significant reduction of CCL4 expression observed in WM cell lines post-BTK inhibitor treatment
  • Macrophage recruitment was reduced in trans-well assays using conditioned media from BTK inhibitor-treated WM cells
  • Phosphorylation of MEK1/2 and its downstream signaling pathways decreased, linking effects to ERK signaling
  • Co-culture with WM cells induced M2-like macrophage phenotype, suggesting bidirectional signaling

Cite This Study

Blackmore et al. (2025) studied this question.

synapsesocial.com/papers/69362f4b4fa91c937236d774https://doi.org/10.1182/blood-2025-1786
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Efficacy and Safety of Bruton Tyrosine Kinase Inhibitors in Waldenström Macroglobulinemia: A Single-Center Retrospective Analysis2026
  2. 2LOX1 expression identifies a population of polymorphonuclear myeloid-derived suppressor cells that are highly enriched in bone marrow samples of treatment-Naïve and BTKi-Relapsed/Refractory WM patients and show constitutive activation of BTK2025
  3. 3Zanubrutinib in the treatment of Waldenström Macroglobulinemia2025 · 1 citations
  4. 4Immune reconstitution with the use of bruton tyrosine kinase inhibitor treatment for patients with Waldenstrom's macroglobulinemia2025
  5. 5Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells2024 · 7 citations