Apolipoprotein B is considered a potential therapeutic drug target for the treatment of AML

Acute myeloid leukemia (AML) faces significant challenges in the development of novel therapeutic strategies due to drug resistance and disease relapse. Therefore, this study aims to identify new therapeutic targets for AML using a drug-target Mendelian randomization approach.

Summary-level data on low-density lipoprotein (LDL)-related traits were obtained from the GWAS data available on the IEU Open GWAS platform, and AML-associated genetic data were sourced from the GWAS Catalog. Seven genes involved in LDL metabolism were selected as potential drug targets: Apolipoprotein A4 (APOA4), Apolipoprotein B (APOB), Apolipoprotein C1 (APOC1), Apolipoprotein E (APOE), Cholesteryl Ester Transfer Protein (CETP), LDL Receptor (LDLR), and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). The inverse-variance weighted (IVW) method was used as the primary analytical approach, with supplementary analyses conducted using MR-Egger regression, weighted median, simple mode, and weighted mode methods to validate the findings.

1. Drug-target Mendelian randomization analysis revealed that lowering LDL levels by targeting and inhibiting APOB may increase the risk of AML, with rs13392272 identified as a potential functional locus in this process. 2. Further validation showed that targeting and inhibiting APOB to reduce its own levels may also increase the risk of AML, with rs693 considered a potential functional locus involved in this effect.