Expression and function of hematopoiesis-stimulating factor receptors on the GPI and GPI hematopoietic stem cells of patients with paroxysmal nocturnal hemoglobinuria/aplastic anemia syndrome.

Paroxysmal nocturnal hemoglobinuria/aplastic anemia (PNH/AA) syndrome presents a markedly increased population of cells deficient in glycophosphatidylinositol (GPI cells) and signs of bone marrow failure, which requires treatment with hematopoiesis-stimulating factors, such as granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). However, little is known about the effects of these stimulating factors on GPI cells. In order to explore the effects of stimulating factors in PNH/AA, G-CSF receptor (CD114) and SCF receptor (CD117) expression levels on GPI and GPI hematopoietic stem cells (HSCs) were measured by flow cytometry (FCM). The mean fluorescence intensity (MFI) values of signal transducer and activator of transcription 5 (STAT5) and phosphorylated (P)-STAT5 were measured in GPI and GPI HSCs by FCM following stimulation with G-CSF or SCF . The expression levels of CD114 and CD117 on GPI HSCs were significantly lower (P<0.01) than those on GPI HSCs in PNH/AA patients and normal controls. The MFI values of STAT5 in the GPI and GPI HSCs of PNH/AA patients and normal controls were not significantly different. However, the MFI values of P-STAT5 in the GPI HSCs of PNH/AA patients were significantly lower than those in the GPI HSCs of PNH/AA patients and normal controls prior to and following stimulation with G-CSF or SCF (P<0.01). The GPI HSCs of PNH/AA patients responded poorly to stimulation by hematopoiesis-stimulating factors, which indicates that these factors can be used safely in patients with PNH/AA.