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December 8, 2025Blood

Age-associated non-mutational resistance in acute myeloid leukemia is driven by DNA damage-induced transcriptional heterogeneity

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Authors

LMLance D. MillerBSBirgit Schilling

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Overview

Murine models reveal DNA damage drives resistance in older acute myeloid leukemia cells and implicates novel therapeutic strategies with BCL2 inhibition.

Key Points

  • Older hematopoietic stem and progenitor cells in acute myeloid leukemia display significant resistance to therapy, particularly to doxorubicin and azacitidine.
  • Hematopoietic stem and progenitor cells from aged mice show marked differences in gene expression profiles compared to younger cells, consistent with clinical observations.
  • Analyses included whole exome sequencing, RNA sequencing, and proteomic profiling, which revealed dysregulation in several DNA damage repair pathways.
  • These findings suggest that aging leads to increased transcriptional heterogeneity in AML, which may contribute to poor treatment outcomes for older patients.

Cite This Study

Miller et al. (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d43fhttps://doi.org/10.1182/blood-2025-639
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Also Consider

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  5. 5Precision Medicine for Older AML Patients2025 · 2 citations