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BIOMARKER:

DNMT3A deletion

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Other names: DNMT3A, DNA Methyltransferase 3 Alpha, DNA (Cytosine-5-)-Methyltransferase 3 Alpha, DNA (Cytosine-5)-Methyltransferase 3A, DNA MTase HsaIIIA, DNA Cytosine Methyltransferase 3A2, DNA Methyltransferase HsaIIIA, DNMT3A2, Dnmt3a
Entrez ID:
Related biomarkers:
2years
Augmented Txnip-p53-p21 axis preserves Dnmt3a mutant hematopoietic stem cells during inflammatory stress (AACR 2022)
Functionally, knocking down Txnip and p21 sensitized Dnmt3aKO HSCs to IFNg-induced cell cycle activation ex vivo. In vivo, down-regulation of p21 had no effect on control HSCs in response to IFNg exposure, but it completely primed Dnmt3aKO and Dnmt3aR878 HSCs to IFNg-associated exhaustion in a transplantation experiment.In summary, our data suggest an augmented Txnip-p53-p21 axis preserves the functional potential of Dnmt3a-mutant HSCs under inflammatory stress, which highlights a novel mechanism to explain the increased fitness of Dnmt3a-mutant HSCs and supports rationale for developing interventions to mitigate expansion of pre-malignant clones as a method of blood cancer prevention.
Late-breaking abstract
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DNMT3A (DNA methyltransferase 1) • IFNG (Interferon, gamma) • TXNIP (Thioredoxin Interacting Protein)
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DNMT3A mutation • DNMT3A deletion