DHCR7 drives AML development through the IL6 / JAK2 / STAT3 signalling pathway

Summary Acute myeloid leukaemia (AML) is a highly heterogeneous haematological malignancy defined by the abnormal proliferation of immature myeloid cells within the bone marrow. 7‐Dehydrocholesterol reductase ( DHCR7 ), a key enzyme in cholesterol metabolism, has been characterized as an oncoprotein in multiple cancer types, yet its functional relevance and underlying mechanisms in AML remain incompletely elucidated. The present study systematically investigated the biological role of DHCR7 in AML pathogenesis. In vitro functional assays demonstrated that either DHCR7 knockdown or treatment with the targeted inhibitor tamoxifen significantly suppressed AML cell proliferation. These inhibitory effects were accompanied by reduced intracellular cholesterol levels, accumulation of 7‐dehydrocholesterol (7‐DHC) and induction of endoplasmic reticulum stress, which ultimately triggered cellular apoptosis. Consistent with in vitro findings, both DHCR7 knockdown and intraperitoneal administration of tamoxifen markedly inhibited leukaemia progression in NSG (NOD Scid Gamma) mouse models, as validated by decreased bioluminescence intensity and reduced Ki‐67 positivity. Mechanistic investigations further revealed that DHCR7 exerts pro‐leukaemic effects through activation of the IL‐6/JAK2/STAT3 signalling axis. Collectively, this study establishes the novel function of DHCR7 in AML pathogenesis and provides robust evidence supporting its potential as a therapeutic target for AML.