Fig. 1: SDH deficiency is a common characteristic of AML and is closely associated with a broad spectrum of drug resistance.

a The mutation rates of SDHx, IDH1/2 and FH in AML. The raw data is sourced from TCGA. *represents AML samples with both FH and SDH mutations. ^△represents AML samples with both FH and IDH mutations. b The expression of SDHx, IDH1/2 or FH in AML samples and normal tissues. c The ratios of the median expression of SDHx, IDH1/2 or FH in different cancer species (T) compared to their corresponding normal tissues (N). The full names of different tumors were listed in the Supplementary table 1. b, c The gene expression data for different cancer species, including AML, was obtained from TCGA, while those for normal tissues were sourced from GTEx. The above data were downloaded from the ‘A combined cohort of TCGA, TARGET, and GTEx samples’ dataset on the UCSC Xena (https://xena.ucsc.edu/). d GSEA enrichment plot for SDH deficiency signaling in drug resistant K562 vs drug sensitive K562. (Data of K562 transcriptome is from GSE131823). SDH deficiency signaling is defined by GSEA’s official “CERVERA_SDHB_TARGETS_1_UP” set. The significance analysis was conducted by two-tailed unpaired Student’s t-test. e, UMAP plot of control (blue; n = 1952) and cytarabine-treated AML cells (orange, n = 2675) (Left). UMAP plot displaying the signature scores for SDH deficiency signaling (Right). (Single-cell RNA-seq data is from GSE146590). f–j The relationship between genes expression or mutation and drug sensitivity in diverse tumor cells. The SDHA^Mut group does not include cells with IDH1/2 mutations, and vice versa for the IDH1/2^Mut group. The (SDH & IDH1/2)^WT group includes cells that do not have mutations in SDH and IDH1/2. Indicated tumor cells with higher-than-average of SDHA expression values were classified into the SDHA^high group, and the opposite were classified into the SDHA^low group. Z scores of anticancer drugs on tumor cells in the same group were averaged and marked by different colors. The T/N ratios of SDHA level were exhibited in Fig. 1f, h. T: tumor; N: normal. RCC includes kidney renal papillary cell carcinoma (KIRP) and kidney renal clear cell carcinoma (KIRC). Source data are provided as a Source Data file.