Effect of PLK4 inhibition by CFI-400945 in K052 cell line purified based on ploidy

Acute myeloid leukemia (AML) with TP53 mutation is a lethal cancer portending the poorest prognosis. We identified PLK4 as a novel therapeutic target by examining its expression and dependence in TP53-mutated AML. Only prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and associated with DNA damage, apoptosis, senescence and polyploidy, while short-term PLK4 inhibition induced DNA damage and triggered p53-dependent apoptosis in TP53-wildtype AML. The study not only shed important light to the pathogenetic role of PLK4, but also led to the development of novel therapeutic strategies in TP53-mutated AML.