Vesicular trafficking is a key determinant of statin sensitivity in AML. (A) Impact of atorvastatin treatment on endocytosis as assessed by uptake of dextran–fluorescein isothiocyanate (FITC) or dextran–Pacific blue (PB) determined by flow cytometry in primary human AML specimens and CD34⁺ cord blood (CB) cells. Results for statin-sensitive specimen 09H113 are representative of 12 primary human AML specimens (supplemental Figure 5). Results for CD34⁺ CB cells are representative of 2 independent experiments performed with CD34⁺ cells isolated from 2 different CB units. Specimen 14H017 was the only statin-resistant specimen among samples tested as part of this study. (B) Enrichment scores of gene sets related to vesicular transport in top 25% statin-sensitive vs -resistant primary human AML specimens of the Leucegene cohort (n = 204). Gene set enrichment analysis (GSEA) was performed with GSEA 4.1.0 software from the Broad Institute using a list of differentially expressed genes between sensitive and resistant specimens ordered based on fold change of expression. (C) Enrichment profiles of top 4 enriched gene sets related to vesicular transport in statin-sensitive compared with statin-resistant specimens. FDR, false discovery rate; GGPP, geranylgeranyl pyrophosphate; IC₅₀, 50% inhibitory concentration; NES, normalized enrichment score; NK, natural killer.