Study Maps How Leukemia Enters Lungs and Identifies Drug Targets

Overview

• Researchers used single-cell and spatial analysis of mouse lung slices and human biopsies to show AML cells cross thin alveolar-capillary walls and leak into lung connective tissue.
• Once in the stroma, leukemia cells trigger fibroblast expansion and scarring that change lung structure and reduce oxygen transfer, helping explain rapid respiratory failure.
• The leukemic lung environment shifts immune cells away from anti-tumor lymphocytes toward immunoregulatory myeloid populations and depletes capillary aerocytes needed for gas exchange.
• The team identified galectin-9 and the interleukin-33 (IL-33) receptor as molecular drivers; blocking either pathway stopped lung infiltration in experiments and a phase 1 trial of a galectin-9 antibody (NCT05829226) is underway.
• A retrospective analysis in the study found patients given prednisone for leukemic lung involvement had marked breathing improvement within 12 hours, suggesting steroids may merit formal evaluation as an early, life-saving treatment while targeted therapies are tested.