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December 8, 2025BloodOpen Access

Peptide-based antagonists for targeting CXCR4 in ibrutinib resistant chronic lymphocytic leukemia

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Authors

HWH WirthRDRashmi Priyadharshini DheenadayalanСНСветлана Новикова

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Overview

Peptide antagonists reduced CXCR4 signaling in chronic lymphocytic leukemia, suggesting a potential strategy to overcome ibrutinib resistance.

Key Points

  • This research investigates the efficacy of peptide-based CXCR4 antagonists in overcoming ibrutinib resistance in chronic lymphocytic leukemia.
  • Analyzed the effects of EPI-X4 derivatives on CLL cell lines and murine models of ibrutinib resistance.
  • Assessed CXCR4 expression and response to CXCR4 antagonists in mouse splenocytes.
  • Measured IC50 values for various peptides in targeted cell lines.
  • Conducted treatment comparisons between ibrutinib and peptide antagonists in Eµ-TCL1 CLL models.
  • The fatty acid-coupled JM#198 peptide showed strong binding to CXCR4 with an IC50 of 27nM, compared to plerixafor's 575nM.
  • Treatment with JM#198 led to a 10-fold reduction in transmigration towards CXCL12 in tumors.
  • CD5+ B cells from ibrutinib treated mice displayed increased CXCR4 expression, not significantly differing from healthy controls.
  • Regulatory T cells normalized to healthy B cell levels after ibrutinib treatment, suggesting it impacts T-cell subsets.

Cite This Study

Wirth et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d8aehttps://doi.org/10.1182/blood-2025-5658
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Also Consider

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

  1. 1Pharmacological inhibition of CXCR4 increases the anti-tumor activity of conventional and targeted therapies in B-cell lymphoma models2025
  2. 2A single-cell multiomics analysis of IRF4 in mediating treatment resistance in ibrutinib-treated chronic lymphocytic leukemia (CLL).2024
  3. 3The Combination of Ibrutinib with BH3 Mimetics or Dichloroacetate Is Effective in B-CLL2025 · 1 citations
  4. 4Abstract 57: Ibrutinib improves chimeric antigen receptor T cell control of leukemia by inhibiting myeloid-derived suppressor cells2024 · 2 citations
  5. 5Abstract 7278: Single-cell RNA-seq analysis reveals distinct tumor and immunosuppressive T-cell phenotypes in CLL patients treated with ibrutinib2026