Metabolic dysfunction-associated steatotic liver disease and acute leukemias - a literature review and future directions.

Metabolic dysfunction-associated steatotic liver (MASLD) is a prevalent cause of chronic liver disease, affecting roughly 38% of adults in the USA. Growing evidence suggests that metabolic conditions such as MASLD and obesity may influence the epidemiology, biology, and clinical outcomes of patients with leukemia. Limited studies indicate that MASLD's pro-inflammatory milieu may contribute to clonal hematopoiesis and leukemogenesis by promoting DNA damage, clonal expansion of mutated hematopoietic stem cells, and providing pro-survival signals. Here we review the current evidence linking MASLD with acute leukemias. We discuss epidemiological trends, mechanistic insights from preclinical and clinical studies, and prognostic implications of MASLD in acute myeloid leukemia and acute lymphoblastic leukemia. We highlight that while metabolic dysfunction appears to adversely impact leukemia outcomes, the interactions are complex and occasionally paradoxical. Finally, we identify key gaps in the literature, underscoring the need for dedicated studies on MASLD in leukemia patients and whether modifying MASLD can improve leukemia outcomes.