SCD and MTHFD2 inhibitors for high‐risk acute myeloid leukaemia patients, as suggested by ELN2017‐pathway association

Since the ‘cell-cyclerelated’ cluster already encompasses a standard regimen drug, cytarabine, we focused on other pathways (Figures 2A–D and S2–S4; Table 1). For the proteomics database, we leveraged Gene Set Variation Analysis (GSVA), originally used for transcriptomic data, to generate pathway scores. MTHFD2 gene expression exhibited a significant increasing trend across ELN2017 risk groups (Figure 2E), and patients with higher gene expression experienced significantly shorter overall survival (Figure 2F). Overall, our study identified risk-associated pathways, target genes and potential synergistic drugs with cytarabine in AML through novel bioinformatic analysis on large multiomic datasets. Since not much is known about the roles of unsaturated fatty acids or folate metabolism in AML, our results could be further exploited to find a mechanistic relationship between those pathways and the malignancy of AML.