PTEN and leukemia: Similarly, hyperactivation of PI3K/AKT signaling in mouse models by inactivation of downstream negative regulators such as Pten, Pml, GSK3β (Yilmaz et al, 2006; Perry et al, 2011; Ito et al, 2012), and FoxO (Tothova et al, 2007) results in a transient increase in activated HSCs and has been reported to be accompanied by exhaustion, impaired repopulation capacity, or leukemia (Yilmaz et al, 2006).