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December 8, 2025BloodOpen Access

BTK inhibition drives mobilization and compartmental shifts of CLL subclones

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Authors

BKBhavna KumarRHRohan HerurLSLaura Samples

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Overview

Analysis reveals BTK inhibitors improved lymphocytosis and altered clonal evolution dynamics in CLL patients, highlighting compartmental shifts in subclones.

Key Points

  • This research aims to investigate shifts in CLL cell compartmentalization upon initiation of BTK inhibitors.
  • Paired PB and LN samples collected from patients starting BTK inhibitor treatment.
  • Whole exome sequencing and bulk RNA sequencing performed on samples from 65 patients.
  • Clonal architecture and cancer cell fractions analyzed using SuperFreq and PyClone-VI.
  • 39% of subclones demonstrated compartmental shifts after BTK inhibitor treatment.
  • Median decrease of 15% in cancer cell fractions was observed in some patients' PB samples on treatment.
  • Not all subclones that increased in PB were detected in sampled LN, indicating heterogeneity.

Cite This Study

Kumar et al. (2025) studied this question.

synapsesocial.com/papers/69362f6c4fa91c937236dfd9https://doi.org/10.1182/blood-2025-7406
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Also Consider

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  1. 1Systematic molecular profiling to identify determinants of response to ibrutinib2025
  2. 2Genomic profiling in CLL patients after BTK inhibitor progression identifies enrichment of mutations in MAPK pathway and epigenetic regulators2025
  3. 3The mutational landscape of resistance to BTK and BCL2 inhibitors in CLL: a real-world multicentric study2026
  4. 4Clonal architecture and growth dynamics of ibrutinib-resistant CLL: Oligoclonal BTK/PLCG2 mutations and emerging non-BTK/PLCG2 drivers2025 · 1 citations
  5. 5Abstract 5828: The genomic architecture of ibrutinib resistance in CLL: Oligoclonal progression with variable anatomical distribution2024