HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285.
Ziwei ZhouLiang ZhongXuan ChuPeng WanWenran DanXin ShaoShuyu ChenZhonghui ZhangYang LuBei-Zhong LiuPublished in: Medical oncology (Northwood, London, England) (2023)
Cytarabine-resistant acute myeloid leukemia (AML) is a common phenomenon, necessitating the search for new chemotherapeutics. WEE1 participates in cell cycle checkpoint signaling and inhibitors targeting WEE1 (WEE1i) constitute a potential novel strategy for AML treatment. HDAC (histone deacetylase) inhibitors have been shown to enhance the anti-tumor effects of WEE1i but molecular mechanisms of HDAC remain poorly characterized. In this study, the WEE1 inhibitor PD0166285 showed a relatively good anti-leukemia effect. Notably, PD0166285 can arise the expression of HDAC11 which was negatively correlated with survival of AML patients. Moreover, HDAC11 can reduced the anti-tumor effect of PD0166285 through an effect on p53 stability and the changes in phosphorylation levels of MAPK pathways. Overall, the cell cycle inhibitor, PD0166285, is a potential chemotherapeutic drug for AML. These fundings contribute to a functional understanding of HDAC11 in AML.
Keyphrases
- acute myeloid leukemia
- histone deacetylase
- cell cycle
- allogeneic hematopoietic stem cell transplantation
- cell proliferation
- poor prognosis
- newly diagnosed
- ejection fraction
- prognostic factors
- signaling pathway
- emergency department
- oxidative stress
- small molecule
- patient reported outcomes
- drug delivery
- dna damage
- long non coding rna
- protein kinase
- binding protein
- risk assessment