Cholesterol Regulator Linked to Aggressive Outcomes in Leukaemia

For patients diagnosed with cytogenetically normal acute myeloid leukaemia (CN-AML), predicting the disease's path is notoriously difficult. As the most heterogeneous subgroup of this blood cancer, it lacks the obvious chromosomal markers found in other variants. However, new research suggests the answer may lie in how cancer cells handle fat. The study identifies Sterol Regulatory Element-Binding Factor 2 (SREBF2)—a master regulator of cholesterol synthesis—as a critical factor in the disease’s aggression.

While SREBF2 typically maintains cholesterol homeostasis in healthy cells, its role becomes sinister when overactive in leukaemia. By analysing a cohort of 185 patients, researchers discovered that overexpression of SREBF2 was significantly associated with adverse overall survival and event-free survival. This correlation remained strong even when stratified across different risk groups.

Using integrated multi-omics analysis—a method combining various biological data sets—the team mapped the molecular chaos caused by this protein. High levels of SREBF2 were linked to the dysregulation of immune pathways, specific DNA methylation changes, and structural variants. Essentially, the protein helps reprogramme the cellular environment to favour leukemogenesis (the development of leukaemia). These findings establish SREBF2 as an essential unfavourable element in CN-AML, offering clinicians a novel biomarker to better assess patient risk and potentially guide future treatment strategies.