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December 8, 2025Cancer Research

Abstract B035: Cell state transitions drive the evolution of disease progression in B-lymphoblastic leukemia

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Authors

SMSadegh MarzbanCGCurtis GravenmierLZLing Zhang

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Overview

Analysis reveals dedifferentiation drives therapy resistance in B-ALL, suggesting new treatment strategies.

Key Points

  • This research investigates the role of cell state transitions in the therapy resistance of B-lymphoblastic leukemia.
  • Analyzed flow cytometry data from bone marrow and peripheral blood samples of B-ALL patients at different stages.
  • Defined major cell states: CD34+/CD38-, CD34+/CD38+, CD34-/CD38+, and CD34-/CD38-.
  • Utilized continuous-time Markov chain modeling to quantify transition rates between states.
  • Applied mechanistic learning to integrate transition dynamics with clinical outcomes.
  • In remission, differentiation rates exceeded dedifferentiation rates, reflecting normal lineage progression.
  • In relapse, dedifferentiation led to restoration of stem-like compartments, indicating greater resistance.
  • Promoting differentiation transiently reduced stem-like fractions but could not prevent relapse.
  • Inhibiting dedifferentiation effectively depleted resistant stem-like clones and improved relapse dynamics.
  • Predictive accuracy for BCR::ABL1 status was 80%, with significant correlations to disease status and minimal residual disease.

Cite This Study

Marzban et al. (2025) studied this question.

synapsesocial.com/papers/693624ce4fa91c937236cf6chttps://doi.org/10.1158/1538-7445.canevol25-b035
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Also Consider

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

  1. 1Cell state transitions drive the evolution of disease progression in B-lymphoblastic leukemia2025 · 2 citations
  2. 2Alternating cycles of quiescent and proliferative cell states determine stemness and leukemia-initiation capacity in acute lymphoblastic leukemia2025
  3. 3Chronic myeloid leukemia (CML) evolution is not encoded in single-cell microstates, but emerges from population-level macrostates2025
  4. 4Chemotherapy selects for myeloid subclones in multiple subtypes of B-cell acute lymphoblastic leukemia2025
  5. 5Dynamics of leukemic blast and immune cell populations in Acute Myeloid Leukemia2025