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December 8, 2025BloodOpen Access

Systematic molecular profiling to identify determinants of response to ibrutinib

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Authors

LLLiang LiSGSatyen GohilTTTuan Tran

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Overview

Systematic molecular profiling reveals distinct evolutionary paths and clonal shifts in CLL patients treated with ibrutinib, suggesting potential markers for treatment response.

Key Points

  • Ibrutinib treatment led to significant clonal shifts in CLL, with 77% of patients exhibiting marked changes post-therapy.
  • Whole-exome sequencing of 169 patients revealed tumor heterogeneity through 579 subclonal clusters.
  • Gene-set enrichment analysis indicates high-risk inflammatory pathways in specific patient subgroups.
  • Identifying patients at risk of progression on BTK inhibitors hinges on understanding distinct mutation-defined subclones.

Cite This Study

Li et al. (2025) studied this question.

synapsesocial.com/papers/69362f4e4fa91c937236d865https://doi.org/10.1182/blood-2025-3881
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Also Consider

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

  1. 1Genomic profiling in CLL patients after BTK inhibitor progression identifies enrichment of mutations in MAPK pathway and epigenetic regulators2025
  2. 2BTK inhibition drives mobilization and compartmental shifts of CLL subclones2025
  3. 3Distinct archetypes of clonal dynamics underlie response and resistance to diverse CLL therapies2025
  4. 4Clonal architecture and growth dynamics of ibrutinib-resistant CLL: Oligoclonal BTK/PLCG2 mutations and emerging non-BTK/PLCG2 drivers2025 · 1 citations
  5. 5Efficacy and prognostic determinants of BTK inhibitors in chronic lymphocytic leukemia (CLL): A real-world single-center cohort study from China2025