Extended Data Fig. 6: Patients with a high MitoScore are predicted to be high responders to VEN plus AraC and not to VEN plus AZA doublet therapy.
(a) Gene set enrichment analysis (GSEA) of the gene ontology biological processes (GOBP) data base at diagnosis in patient receiving the duplet therapy venetoclax plus low dose acracytine (LDAC) from the study VIALE-C (NCT03069352). RNA-seq data available through the European Genome-phenome Archive (EGAS00001003820). Dotted line at −1.3 (log10(0.05)) indicates the threshold limit of the q-value below which the gene signatures are significantly enriched. (n=19 patients). (b–d) Kaplan-Meier plots of overall survival (OS) for patients with AML treated with venetoclax in association with LDAC (n=19 patients) based on two different OxPHOS score category (MOOTHA_MITOCHONDRIA geneset, B; FARGE_HIGH_OXPHOS geneset, C, and FAO score category (FATTY_ACID_METABOLISM geneset, D). Data analysis is by log-rank Mantel-Cox’s t-test. (e) Heatmap of gene-expression values depicting CPT1a and BCL2 family members in AML patients treated with venetoclax in association with LDAC (n=19 patients) and classified either by their MitoScore (Low vs High) or by their initial response (CR+CRi vs RD). Low to high expression is represented by a change of colour from orange to green, respectively. (f) OncoPrint of genetic alterations in patients with AML treated with venetoclax in association with either LDAC (VIALE-C, n=19 patients) or HMA (VIALE-A, n=12 patients) classified in MitoScoreLow and MitoScoreHigh. (g) Data of oxygen consumption rate (OCR) in the primary sample TUH161. (n=1 with 3 technical replicates). Representation of the spare respiratory capacity (SRC) calculation.
