DEFECTIVE EXPRESSION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INTERLEUKIN-3/INTERLEUKIN-5 RECEPTOR COMMON BETA-CHAIN IN CHILDRENWITH 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 beta chain (beta c) i s a cause of fatal respiratory failure, beta c 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 l eukemia (AML). In mice, the PAP phenotype was generated by targeted de letion of the gene for pc and can be treated by transplantation of wil d-type bone marrow into beta c -/- mice, Thus, our findings in beta c -/- mice provide evidence for a causal relationship between the lung d isease and the hematopoietic system. We describe here expression defec ts of beta c or beta c plus GM-CSF receptor or chain (GM-CSFR cu) in 3 pediatric patients with AML and PAP symptoms. All of the patients' le ukemic cells failed to express normal levels of beta c, The leukemic c ells of patients no. 2 and 3 additionally lacked the expression of GM- CSFR alpha, as shown by flow cytometry. Strikingly reduced or absent f unction of pc was demonstrated in clonogenic progenitor assays with ab sent colony-forming unit (CFU) growth after GM-CSF or IL-3 stimulation . The response to growth factors acting via a growth factor receptor d istinct from the GM-CSF/IL-3/IL-5 system (recombinant human granulocyt e colony-stimulating factor [rhG-CSF]) was normal. After antileukemic treatment, the pulmonary symptoms resolved and beta c or beta c plus G M-CSFR a expression was normal, Our findings provide evidence that a d efect in the expression of beta c or beta c plus GM-CSFR alpha on AML blasts can be associated with respiratory failure in patients with AML , (C) 1998 by The American Society of Hematology.