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December 8, 2025Blood

Replicative stress-induced aging of hematopoietic stem progenitor cells increases oncogenic mutation burden and incidence of myelodysplasia in sickle cell disease mice

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Authors

MCMengna ChiFLFabienne LucasTSTahereh Setayesh

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Overview

Research shows increased oncogenic mutations in hematopoietic stem cells of sickle cell disease mice, suggesting early intervention could mitigate risks of myelodysplastic syndrome.

Key Points

  • This research investigates the effects of replicative stress on hematopoietic stem progenitor cells in sickle cell disease and its association with myelodysplastic syndrome.
  • Analyzed hematopoietic stem progenitor cells from sickle cell disease and normal mice via whole exome sequencing.
  • Conducted quarterly monitoring of peripheral blood and flow cytometry.
  • Transplanted bone marrow cells into wild-type mice and sequenced pre- and post-transplant samples.
  • Sickle cell disease mice showed increased aging-related oncogenic mutations compared to normal controls.
  • Myeloid-biased hematopoiesis was observed in sickle cell disease mice from an early age.
  • Higher mutation burden in sickle cell disease hematopoietic stem cells linked to increased risk of myelodysplastic syndrome.

Cite This Study

Chi et al. (2025) studied this question.

synapsesocial.com/papers/69362f714fa91c937236e18chttps://doi.org/10.1182/blood-2025-11
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Also Consider

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

  1. 1Premature senescence impairs hematopoietic stem cell function during sickle cell disease in mice and humans2026 · 2 citations
  2. 2HbSS mice accumulate mitochondrial DNA mutations at a significantly higher rate than HbAA and HbAS mice2025
  3. 3Sf3b1+/K700E hematopoietic stem cells create their own expansion niche2025
  4. 4Abstract LB227: Accelerated intra-clonal transcriptomic diversification of hematopoietic stem cells during aging fuels leukemia evolution2024 · 1 citations
  5. 5Disproportionate risk of hematologic malignancies in sickle cell disease (SCD) across age strata: A multicenter matched cohort analysis2025