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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

Observational analysis found increased oncogenic mutations in sickle cell disease mice, suggesting early myeloid bias and aging hematopoietic stem cells.

Key Points

  • Increased oncogenic mutation burden presents as replication stress accelerates aging in sickle cell disease mice.
  • Analysis identified a significant rise in mutations from 1.2% to 2.3% in SCD mice, indicating a heavy mutation load.
  • Assessment using targeted deep DNA sequencing revealed heightened mutation occurrence in hematopoietic stem cells.
  • Findings highlight a critical need for early interventions targeting sickle cell disease to mitigate risks of hematological malignancy.

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. 4Disproportionate risk of hematologic malignancies in sickle cell disease (SCD) across age strata: A multicenter matched cohort analysis2025
  5. 5Identification of two distinct human hematopoietic stem cell subsets and their age-dependent dynamics by single-cell multi-omics2025 · 1 citations