Extended Data Fig. 7: Single-cell transcriptomic analysis confirms the enrichment of lipids-related gene signatures in AraC-specific residual cell clusters. | Nature Cancer

Extended Data Fig. 7: Single-cell transcriptomic analysis confirms the enrichment of lipids-related gene signatures in AraC-specific residual cell clusters.

From: Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia

Extended Data Fig. 7: Single-cell transcriptomic analysis confirms the enrichment of lipids-related gene signatures in AraC-specific residual cell clusters.The alternative text for this image may have been generated using AI.

(a,b) Cumulative total cell tumor burden of human viable CD45+CD33+CD44+ AML cells for PDX TUH07 (A) and TUH69 (B) was assessed in bone marrow and spleen at day 0 (D0) and at day 8 (D8) for the three different treatments by flow cytometry. Data are assessed post in vivo treatment with venetoclax (100 mg/kg) and aracytine (30 mg/kg). Data are displayed as mean ± s.e.m. TUH07, D0 n=4 mice, VEN n=6, AraC n=5 mice, VEN+AraC n=6 mice; TUH69, D0 n=5 mice, VEN n=5, AraC n=5 mice, VEN+AraC n=8 mice. P values: TUH07, D0/VEN **P=0.0095, D0/AraC *P=0.0159, D0/VEN+AraC **P=0.0095, AraC/VEN+AraC **P=0.0043; TUH69, D0/VEN P=0.1508, D0/AraC P=0.3095, D0/VEN+AraC **P=0.0016, AraC/VEN+AraC **P=0.0451. Data analysis in A and B is by two-tailed unpaired Student’s t-test with Welch’s correction for unequal variance. *P < 0.05, **P < 0.01, ****P < 0.0001, ns:non-significant. (c) Unsupervised hierarchical clustering was done by principal component analysis (PCA) in PDX TUH07 and TUH69. 9 different clusters were identified. (d) UMAP visualization of single cell from PDX TUH07 and TUH69 colored per patient (n=31,604 cells). (e) Visualization of the repartition of the total cell count per cluster with distinction of cells coming from each PDX. (f) Visualization of the repartition of the total cell count per cluster with the different conditions highlighted (Day0; Day8 following VEN; AraC; VEN plus AraC). (g) Visualization of single cell scores for CD36 gene enrichment on violin plots. The center line represents the median (Q2) and the box spans the 25th (Q1) to 75th percentiles (Q3). Minimum (Q0) and maximum (Q4) values are outside the box. D0 (Q0: −4.2108; Q1: −0.9785; Q2: 0.347; Q3: 2.3348; Q4: 5.1356), VEN (Q0: −2.7858; Q1: 0.669; Q2: 2.4531; Q3: 3.0013; Q4: 5.2046), AraC (Q0: −2.9885; Q1: −0.454; Q2: 1.8428; Q3: 3.0775; Q4: 5.019), VEN+AraC (Q0: −1.5777; Q1: 1.0628; Q2: 2.2119; Q3: 2.8247; Q4: 4.7953). (h,i) Visualization on the UMAP plot of single cell scores for OxPHOS gene signature enrichment. (H) and fatty acid metabolism gene signature enrichment (I) using Single-Cell Signature Explorer.

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