Here we show that blocking TNFR2 but not TNFR1 selectively inhibits MPN cells over normal controls and implicate X-linked inhibitor of apoptosis (XIAP), cIAP and mitogen-activated protein kinase 8 (MAPK8) as key mediators of differential responses to TNF. The gene discussed is TNFRSF1B; the disease is myeloproliferative neoplasm.