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December 8, 2025BloodOpen Access

A collective non-mutational transition governs the development of chronic myeloid leukemia

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Authors

RERichard Van EttenNJNilamani JenaJLJoan Liu

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Overview

Mathematical modeling demonstrates hematopoietic stem cell interactions drive myelopoiesis and leukemia in chronic myeloid leukemia.

Key Points

  • This research aims to explore how collective non-mutational events govern chronic myeloid leukemia development.
  • Developed a conditional BCR::ABL1 transgenic mouse model to study CML pathogenesis.
  • Created bone marrow chimeras to analyze the effects of BCR::ABL1+ HSC in a non-perturbed environment.
  • Utilized doxycycline to induce BCR::ABL1 expression in chimeras.
  • Chimeras with 10% HSCL developed CML-like leukemia after 2-3 months, while 90% HSCL showed no latency period.
  • A threshold of ~4% HSCL chimerism was needed for leukemia development, below which mice resembled treatment-free remission.
  • Mathematical modeling accounted for threshold, latency, and CML development stochasticity.

Cite This Study

Etten et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd5fhttps://doi.org/10.1182/blood-2025-1984
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Also Consider

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

  1. 1Abstract 2307: State-transition modeling of blood transcriptome predicts disease evolution and treatment response in chronic myeloid leukemia (CML)2024 · 1 citations
  2. 2GENETIC ASPECTS OF CHRONIC MYELOID LEUKEMIA: FROM FUNDAMENTAL MECHANISMS TO CLINICAL PRACTICE2025
  3. 3Understanding drug resistance in chronic myeloid leukemia through the lens of leukemic stem cell states: insights from single-cell analyses2026 · 2 citations
  4. 4Abstract 6830: State-transition model of time-series single-cell RNA-seq identifies gene-level origins of disease microstate stability in chronic myeloid leukemia (CML).2026
  5. 5Computational modeling reveals key factors driving treatment-free remission in chronic myeloid leukemia patients2024