NSD2 and mantle cell lymphoma: Gain-of-function mutations (E1099K and T1150A) in the SET domain of NSD2 have been associated with the enhanced enzymatic activity of NSD2 in mantle cell lymphoma and pediatric acute lymphoblastic leukemia, in which they cause destabilization of the auto-inhibitory loop responsible for keeping signaling in check (refer below) [108, 109].