Ascorbate Inhibits Proliferation and Promotes Myeloid Differentiation in TP53-Mutant Leukemia
Carlos C Smith-Diaz, Nicholas J Magon, Judith L McKenzie, Mark B Hampton, Margreet CM Vissers, Andrew B Das
FRONTIERS IN ONCOLOGY | FRONTIERS MEDIA SA | Published : 2021
Loss-of-function mutations in the DNA demethylase TET2 are associated with the dysregulation of hematopoietic stem cell differentiation and arise in approximately 10% of de novo acute myeloid leukemia (AML). TET2 mutations coexist with other mutations in AML, including TP53 mutations, which can indicate a particularly poor prognosis. Ascorbate can function as an epigenetic therapeutic in pathological contexts involving heterozygous TET2 mutations by restoring TET2 activity. How this response is affected when myeloid leukemia cells harbor mutations in both TET2 and TP53 is unknown. Therefore, we examined the effects of ascorbate on the SKM-1 AML cell line that has mutated TET2 and TP53. Susta..View full abstract
This study was supported by funding from the Canterbury Medical Research Fund, the Bone Marrow Cancer Research Trust, and a NZSO Roche Translational Cancer Research Fellowship to AD.