Meta-Biol

• Pathways

NOX4 catalyzes the synthesis of H2O2 downstream of FLT3 ITD mutants in a STAT5-dependent manner, increasing the levels of reactive oxygen species (ROS) (Jayvavelu et al, 2016a; Sallmyer et al, 2008; Reddy et al, 2011). High ROS levels cause oxidative inactivation of the protein tyrosine phosphatase PTPRJ, also known as DEP1, a negative regulator of FLT3 signaling. In consequence, FLT3 ITD-expressing cells have higher signaling activity than the wild type, as well as increased proliferation (Arora et al, 2011; Godfrey et al, 2012; Kresinsky et al, 2015; Jayavelu et al, 2016a; reviewed in Jayavelu et al, 2016b).