Alterations in metabolic gene signatures in primitive quiescent leukemia stem cells in response to TKI treatment. (A-B) Dot plots showing enrichment of metabolism-related gene sets (A) and hallmark gene sets (B) in the qHSC cluster, comparing cells treated with nilotinib for 2 days (Nil 2d) with vehicle (Veh) (left), with nilotinib for 2 weeks (Nil 2w) vs vehicle (middle), or with nilotinib for 2 weeks vs 2 days (right). NES and statistical significance (FDR) are represented by color and size, respectively. (C) Dot plot showing expression of genes within metabolic pathways in CML qHSC, treated with Veh, Nil 2d, and Nil 2w. The statistical significance (FDR) and fraction of cells expressing the gene are represented by color and size, respectively. (D) uMAP showing the expression of Hk1, Hk2, Pdk1, and Slc2a3 in CML LSK cells treated with vehicle, Nil 2d, or Nil 2w. (E) Enrichment of the HIF-1 regulon in CML qHSC treated with Nil 2d or Nil 2w compared with Veh, based on pySCENIC analysis. (F) The percentage of HIF-1α–expressing normal LTHSCs, CML LTHSCs treated with vehicle, and CML LTHSCs treated with Nil (TKI) for 2 weeks in normoxic or hypoxic conditions (n = 3-4). Significance values: ∗P < .05. Results represent mean ± SEM of multiple replicates.