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Leucine, Autoimmune Diseases, and Circulating Mediators Shape the Causal Landscape of Lymphoid Malignancies

GSE322478 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/04/12 Platform GPL33758
Summary
This study investigated environmental and metabolic determinants of lymphoid malignancies (LM) using a systematic Mendelian randomization analysis of 10,090 GWAS traits from the IEU OpenGWAS database. Autoimmune diseases, including hyperthyroidism and membranous nephropathy, were identified as risk factors for LM, and mediation analysis suggested circulating promotilin, monounsaturated fatty acids, and glucose as potential mediators. Leucine was identified as a protective factor. Findings were evaluated in large epidemiological cohorts and UK Biobank multi-omics data, and further examined in lymphoid malignancy cell lines and an MH/NRASG12D B-cell precursor acute lymphoblastic leukemia mouse model. High-leucine conditions suppressed cell proliferation and induced apoptosis in vitro, while a high-leucine diet prolonged survival in vivo. Higher plasma leucine levels were also associated with improved clinical outcomes in B-ALL and CAR-T-treated B-cell lymphoma cohorts.
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Also filed as BioProject PRJNA1429416 and SRA study SRP679877. Searching any of these in the dataset finder brings you back here.

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