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

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.