NEW YORK — A study led by NYU Langone Health researchers, published online on June 29, 2026, in Nature Immunology, identified specific molecular targets that reduce acute myeloid leukemia (AML) cell infiltration in the lungs. AML is a cancer characterized by the abnormal multiplication of bone marrow cells that typically develop into blood cells.

Researchers examined lung tissue slices from mice and tissue biopsies from patients diagnosed with AML lung involvement. The study concluded that AML cancer cells infiltrate the lungs by passing through thin alveolar wall blood vessels and then leaking into the connective tissue, known as stroma. This infiltration of AML cells led to an increase in fibroblasts within the stroma, which results in fibrotic, scarlike tissue that obstructs breathing.

The study also found that structural changes driven by AML resulted in a shift in lung immune cells, moving away from lymphocytes and toward myeloid cells. Additionally, the presence of AML cells was associated with a drop in the number of endothelial capillary aerocytes in the lungs. "There has been a lack of understanding in our field as to how leukemia cells invade the lungs, why they trigger respiratory crises, and why steroids counter this to some degree," said Iannis Aifantis, chair of the Department of Pathology at NYU Grossman School of Medicine.

The research identified galectin-9 and the interleukin-33 (IL-33) receptor protein as key drivers of lung inflammation in AML. The study demonstrated that blocking either galectin-9 or IL-33 receptor signaling prevents the infiltration of AML cells into the lungs. "Our results describe for the first time specific molecular targets that reduce lung infiltration, which new, better-tailored drug classes can be designed against," Aifantis said.

Researchers also analyzed past AML cases and observed that patients treated with prednisone for breathing crises showed 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, an instructor in the Department of Pathology at NYU Grossman School of Medicine. A Phase 1 clinical trial (NCT05829226) is currently evaluating an antibody treatment that targets galectin-9 for AML.

The American Cancer Society estimates that 23,000 people will be diagnosed with AML in 2026, and approximately 11,500 people will die from the disease in the same year. This research received support from several National Institutes of Health grants. Aifantis serves as a consultant for Forsite Labs, and Aristotelis Tsirigos is a scientific adviser to Intelligencia AI. Paraskevopoulou said the next step is to determine whether combining galectin-9 blockade with standard chemotherapy or targeted therapies provides added value in clinical settings.

Why It Matters

This study provides insight into the mechanisms by which acute myeloid leukemia (AML) affects lung function, addressing a prior gap in understanding how leukemia cells invade the lungs and contribute to respiratory issues. The identification of specific molecular targets, galectin-9 and IL-33 receptor, offers potential avenues for the development of new treatments. The findings also suggest that early steroid treatment, previously based on physician judgment, could become a standardized guideline for managing respiratory complications in AML patients.