(A) Neoplastic evolution demonstrates convergence, from disparate genetic origins toward a common destination of myeloblasts bearing gross molecular and morphologic similarities. (B) Heatmap shows CXCR2 expression (exp.) in primary AML cells categorized by morphology (M0-M7) (TCGA, n = 171, RNA sequencing). The color coding beneath indicates a subset of contained recurrent mutations and chromosome translocations (some of which are known as first hits). Gene expression by RNA sequencing. (C) Cxcr2 expression is dramatically upregulated in the immediate committed progeny (MPP) of normal HSCs. The implication is that broadly relevant nononcogene therapeutic targets of opportunity such as CXCR2 likely reflect a common theme in neoplastic evolution: transformation in committed progenitors despite origin of the first hit in HSCs or the germline. Box-and-whiskers plot data are expressed as median ± range. P = .007, Mann-Whitney test. CLP, common lymphoid progenitor; CMP, common myeloid progenitor; MMP, multipotent myeloid progenitor (public data E-MTAB-2262).