Study reveals how leukemia cells invade lungs and cause breathing problems

Study reveals how leukemia cells invade lungs and cause breathing problems

Researchers at NYU Langone Health have identified the mechanisms by which blood cancer cells enter the lungs, damage tissue, and trigger severe respiratory failure. The study, published June 29, 2026, in Nature Immunology, focuses on acute myeloid leukemia (AML), a condition where bone marrow cells that should become blood cells instead multiply abnormally.

Respiratory failure is a common early complication of AML, but the biological process has been poorly understood. Researchers stated that reducing these early breathing crises is essential to allow AML therapies sufficient time to work.

The Process of Lung Infiltration

By analyzing tissue biopsies from AML patients and lung tissue slices from mice, the research team discovered that AML cells enter the lungs through blood vessels in the thin alveolar wall. Once these cells leak into the connective tissue, known as the stroma, they alter its structure.

The cancer cells increase the number of fibroblasts, which produce the collagen necessary for the elasticity and strength required for breathing. In AML patients, these cells become overactive, creating fibrosis—scarlike tissue that hinders the ability to breathe.

The study further revealed that these structural changes disrupt the lung's immune environment. There is a shift away from lymphocytes, which attack cancer cells, toward myeloid cells that decrease the immune attack. Additionally, the presence of AML cells leads to a significant drop in endothelial capillary aerocytes, the cells responsible for supplying oxygen to the bloodstream.

Molecular Drivers and Treatment

Using single-cell and spatial transcriptomics to map gene activity and cellular diversity, the team identified two proteins driving the widespread lung inflammation:

• Galectin-9: A protein that binds sugar molecules on cell surfaces to facilitate communication. The study found AML cells produce more galectin-9 due to cell-cell interactions and inflammation in the lungs.
• Interleukin-33 (IL-33) receptor protein: Located on the surface of leukemia cells, this protein passes on signals in damaged lung tissue. Higher-than-normal levels of IL-33 receptor signaling were observed in AML patients.

The researchers demonstrated that blocking either of these pathways stops AML cells from infiltrating the lungs. A phase 1 clinical trial (NCT05829226) is currently testing a first-of-its-kind antibody treatment targeting galectin-9 to combat AML.

The study also analyzed past cases regarding the use of steroids. While doctors often used steroids based on experience or guesses, the researchers found that all patients treated with prednisone during a breathing crisis caused by leukemic lung infiltration 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 judgement calls to a treatment guideline in the field that saves lives,"

Varvara Paraskevopoulou, PhD, instructor in the Department of Pathology at NYU Grossman School of Medicine, via NYU Langone Health

Broader Context of Leukemia and Lung Health

Lung complications in leukemia can stem from various sources. These include pulmonary hemorrhage, which is often linked to low platelet counts.

Treatment-related damage also plays a role. Chemotherapy can cause pneumonitis or pulmonary fibrosis, while stem cell transplants may lead to graft-versus-host disease (GVHD) and bronchiolitis obliterans.

The American Cancer Society estimates that 23,000 people will be diagnosed with AML in 2026, with 11,500 expected deaths.

According to Iannis Aifantis, PhD, chair of the Department of Pathology at NYU Grossman School of Medicine, the results describe specific molecular targets that can be used to design better-tailored drug classes.

The research team's next objective is to determine if combining the blockade of galectin-9 with targeted therapies or standard chemotherapy provides additional value in clinical settings.