Targeting DNA Damage Repair Functions of Two Histone Deacetylases, HDAC8 and SIRT6, Sensitizes Acute Myeloid Leukemia to NAMPT Inhibition.
Pu ZhangLindsey T BrintonKatie WilliamsSteven SherShelley J OrwickLai Tzung-HueiAlice S MimsChristopher C CossSamuel K KulpYoussef YoussefWing Keung ChanShaneice R MitchellAllison MustonenMatthew CannonHannah PhillipsAmy M LehmanTierney KauffmanLarry BeaverDaniel CanfieldNicole R GrieselhuberLapo AlinariDeepa SampathPearlly YanJohn C ByrdJames S BlachlyRosa LapalombellaPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2021)
Our findings provide evidence that HDAC8 inhibition- or shSIRT6-induced DNA repair deficiencies are potently synergistic with NAMPT targeting, with minimal toxicity toward normal cells, providing a rationale for a novel-novel combination-based treatment for AML.
Keyphrases
- dna repair
- dna damage
- acute myeloid leukemia
- oxidative stress
- induced apoptosis
- cancer therapy
- diabetic rats
- histone deacetylase
- dna damage response
- allogeneic hematopoietic stem cell transplantation
- dna methylation
- high glucose
- cell cycle arrest
- endoplasmic reticulum stress
- clinical trial
- ischemia reperfusion injury
- signaling pathway
- drug delivery
- drug induced
- gene expression
- cell death
- combination therapy
- cell proliferation
- endothelial cells
- replacement therapy