Figure 8.

Proposed mechanisms by which SAMHD1 regulates AML cell proliferation in vitro and affects tumorigenicity in xenografted mice. Silencing of SAMHD1 in AML-derived THP-1 cells causes down-regulation of PTEN and increase of PI3K activity, which in turn induces phosphorylation of Akt and of its substrate p27. Phosphorylation of p27 at residue T157 results in its mis-localization to the cytoplasm and impairment of its CDK inhibitory function, leading to increased cell proliferation and enhanced cell migration. The letters P with a circle indicates phosphorylation of Akt and p27. In contrast, SAMHD1 KO attenuates THP-1 cell tumorigenicity in xenografted immunodeficient mice, possibly due to increased TNF-α expression and inflammation responses in tumors.