A study led by NYU Langone Health researchers reveals how blood cancer cells enter the lungs, damage tissue, and cause severe breathing problems in patients with acute myeloid leukemia (AML), according to a June 29 publication in Nature Immunology.
The research focused on understanding respiratory failure, a common early complication of AML caused by cancer cells infiltrating the lungs. The team examined lung tissue from mice and biopsies from patients with AML lung involvement. They found that AML cells pass through alveolar wall blood vessels into connective tissue, where they increase fibroblast numbers. This process leads to excessive collagen production and scarlike fibrosis that hinders breathing.
Tests showed that these structural changes shift the immune cell balance in the lungs away from lymphocytes, which attack cancer cells, toward myeloid cells that suppress immune response. There was also a significant drop in endothelial capillary aerocytes—cells crucial for oxygen exchange—in affected lungs.
Analysis of past cases indicated that steroid treatment is often used when patients experience breathing crises due to leukemic infiltration. The researchers reported all patients treated with prednisone during such episodes showed dramatically improved respiratory function within 12 hours. "Our results provide first-time evidence that early steroid treatment should go from something that doctors try based on judgment calls to a treatment guideline in the field that saves lives," said Varvara Paraskevopoulou, PhD, an instructor at NYU Grossman School of Medicine.
The team used single-cell transcriptomics and spatial transcriptomics to map genetic activity and cellular interactions within leukemic lung tissue. They identified two proteins driving inflammation: galectin-9—which helps cell communication—and interleukin-33 (IL-33) receptor protein on leukemia cells. Blocking either pathway prevented further infiltration of AML cells into the lungs by affecting both immune and cancer cell behavior. A phase 1 clinical trial is currently testing an antibody therapy targeting galectin-9 for potential use against AML.
According to Paraskevopoulou, "Our next step is to determine whether combining galectin-9 blockade with standard chemotherapy or targeted therapies provides added value in clinical settings."
