Model of cytokine-mediated rescue. FLT3-ITD stimulates both proliferation and cell survival. FLT3 inhibitors are able to inhibit both cellular processes. Redundant survival signaling is mediated through a JAK2-STAT5-PIM pathway downstream of the GM-CSF or IL-3 receptor. Inhibition of cell survival requires blockade of both FLT3-ITD and cytokine signaling with either ruxolitinib or INCB053914. INCB053914 is a pan-PIM inhibitor; however, our data only support a physiologic role for PIM1/2 in the role of cytokine-mediated rescue of cells from FLT3 inhibition (FLT3i).