KIT D816V promotes clonal mast cell expansion and resistance to TNF. The KIT D816V mutation in mast cells induces secretion of TNF and upregulation of the BIRC5 gene, promoting mast cell survival and a growth advantage compared with nonmutated cells. A microenvironment with high TNF levels suppresses myelopoiesis and selectively promotes clonal expansion of mast cells with the KIT D816V mutation. Purple cells indicate KIT D816V mutated cells, and orange cells indicate wild-type cells. Elevated serum TNF levels in patients with systemic mastocytosis are associated with worse overall survival (the graph is adapted from Figure 5C in the article by Greiner et al that begins on page 1006). Professional illustration by Somersault18:24.