WT1 inhibits AML cell proliferation in a p53-dependent manner

WT1 has been reported to function as an oncogene and a tumor suppressor in acute myeloid leukemia (AML). The molecular mechanisms have not yet been fully elucidated. Here, we report that p53, served as a tumor suppressor, plays a critical role in regulating the function of WT1 in AML. For details, we performed a meta-analysis on 1131 AML cases, showing that WT1 gene mutation and TP53 gene exhibited a mutually exclusive predisposition in AML. p53 can be recruited to the promoter region of WT1's target genes to modulate their expression by physically interacting with WT1. The AML-derived p53 mutation (p53(R248Q)) can disrupt the interaction between WT1 and p53, resulting in the loss of modulation of WT1's target genes. Furthermore, wild-type p53 maintained the anti-proliferation activity of WT1 in AML cells. In contrast, WT1 promoted AML cell proliferation in the absence of p53 (or mutated p53). In conclusion, we demonstrated a novel explanation of the controversial function of WT1 in AML. These results provided a mechanism by which WT1 inhibited AML cell proliferation in a p53-dependent manner.

Automated summary

WT1 functions as an oncogene and tumor suppressor in AML, with p53 playing a critical role in regulating WT1's function. P53 interacts with WT1 to modulate the expression of WT1's target genes. AML-derived p53 mutation can disrupt this interaction, leading to loss of modulation of WT1's target genes.