Defective expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 receptor common β chain in children with acute myeloid leukemia associated with respiratory failure

Deficiency of the granulocyte-macrophage colony-stimulating factor (GM- CSF)/interleukin-3 (IL-3)/IL-5 receptors common β chain (βc) is a cause of fatal respiratory failure. βc deficiency manifests as pulmonary alveolar proteinosis (PAP). PAP has heterogenous etiologies that may be genetic or aquired. Some cases of PAP have been reported to be associated with hematologic malignancies such as acute myeloid leukemia (AML). in mice, the PAP phenotype was generated by targeted deletion of the gene for βc and can be treated by transplantation of wild-type bone marrow into βc -/- mice. Thus, our findings in βc -/- mice provide evidence for a causal relationship between the lung disease and the hematopoietic system. We describe here expression defects of βc or βc plus GM-CSF receptor α chain (GM-CSFR α) in 3 pediatric patients with AML and PAP symptoms. All of the patients' leukemic cells failed to express normal levels of βc. The leukemic cells of patients no. 2 and 3 additionally lacked the expression of GM-CSFR α, as shown by flow cytometry. Strikingly reduced or absent function of βc was demonstrated in clonogenic progenitor assays with absent colony-forming unit (CFU) growth after GM-CSF or IL-3 stimulation. The response to growth factors acting via a growth factor receptor distinct from the GM-CSF/IL-3/IL-5 system (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was normal. After antileukemic treatment, the pulmonary symptoms resolved and βc or βc plus GM-CSFR α expression was normal. Our findings provide evidence that a defect in the expression of βc or βc plus GM-CSFR α on AML blasts can be associated with respiratory failure in patients with AML.