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December 8, 2025Blood

Distinct archetypes of clonal dynamics underlie response and resistance to diverse CLL therapies

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Authors

CJConnor JohnsonETEugen TauschSRSandra Robrecht

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Overview

Longitudinal analysis reveals distinct clonal dynamics and genetic resistance patterns in CLL therapies, indicating implications for treatment strategies.

Key Points

  • This research investigates the clonal dynamics and genetic determinants affecting response and resistance in chronic lymphocytic leukemia (CLL) therapies.
  • Conducted longitudinal analyses on 107 patients with CLL using various therapies.
  • Monitored measurable residual disease (MRD) alongside genetic characterization from blood samples.
  • Employed ultra-deep sequencing and phylogenetic tree analysis to identify subclonal variations.
  • Utilized Markov Chain Monte Carlo to model clonal dynamics during treatment.
  • Identified four clonal archetypes characterizing patient responses to therapies.
  • Observed mutational differences in therapy-resistant subclones, impacting relapse.
  • Described genetic heterogeneity in response to venetoclax-obinutuzumab therapy.

Cite This Study

Johnson et al. (2025) studied this question.

synapsesocial.com/papers/69362f5d4fa91c937236dc71https://doi.org/10.1182/blood-2025-245
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