Neutrophil-specific reduction in the expression of granulocyte-macrophage colony-stimulating factor receptor subunits in myelodysplastic syndromes

The proliferative and differentiative response of neutrophils to granulocyt e-macrophage colony-stimulating factor (GM-CSF) is known to be impaired in patients with myelodysplastic syndromes (MDS). To investigate the mechanism s of the defective response in MDS, we examined expression levels of GM-CSF receptor alpha (GMR alpha) and common beta (betac) subunits on CD16(+) neu trophils, CD14(+) monocytes and CD3(+) T cells from 26 MDS patients and 10 healthy controls using flow cytometry. Expression of GMR alpha was signific antly decreased on the neutrophils of five out of 26 patients and was not s pecific for any FAB subtype. In contrast, betac expression on neutrophils w as significantly reduced in 14 out of 26 patients with a higher proportion occurring in the advanced stages of MDS including refractory anaemia with e xcess of blasts (RAEB), RAEB in transformation (RAEBt) and overt leukaemia compared with refractory anaemia (RA)/RA with ringed sideroblasts (RARS) or healthy controls. Decreased betac also correlated with the degree of hypog ranular neutrophil morphology and increased infection. Expression of both s ubunits on T cells and monocytes in MDS was similar to normal controls. Pol ymerase chain reaction amplification of reverse-transcribed mRNA isolated f rom the affected neutrophils suggests that the reduction of betac may resul t from decreased message levels. The observed reduction in GM-CSF receptor expression could account for the impaired proliferative and maturational re sponses in MDS.