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. 2016 May;11(5):1668-1672.
doi: 10.3892/etm.2016.3163. Epub 2016 Mar 15.

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

Rong Fu  1 , Shao-Xue Ding  1 , Y I Liu  1 , Li-Juan Li  1 , Hui Liu  1 , Hong-Lei Wang  1 , Tian Zhang  1 , Zong-Hong Shao  1
Affiliations

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

Rong Fu et al. Exp Ther Med. 2016 May.

Abstract

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 in vitro. 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.

Keywords: CD114; CD117; STAT5; anemia; aplastic; hematopoietic stem cell; hemoglobinuria; paroxysmal.

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Figures

Figure 1.
Figure 1.
(A) Expression of CD114 on the (Aa) GPI+ and GPI− cells of patients with PNH and (Ab) GPI+ cells of normal controls. (B) Expression of C117 on the GPI+ and GPI− cells of (Ba) patients with PNH and (Bb) normal controls. (C) Percentage of CD114 or C117 expression on GPI+ and GPI− cells isolated from the bone marrow. CD, cluster of differentiation; CD114, granulocyte colony-stimulating factor receptor; CD117, stem cell factor receptor; GPI, glycophosphatidylinositol; PNH, paroxysmal nocturnal hemoglobinuria.
Figure 2.
Figure 2.
(A) MFI of STAT5 in the (Aa) GPI+ and GPI− cells of PNH patients and (Ab) GPI+ cells of normal controls. (B) Percentage of STAT5 in GPI+ cells and GPI− cells of the bone marrow. MFI, mean fluorescence intensity; STAT5, signal transducer and activator of transcription 5; GPI, glycophosphatidylinositol; PNH, paroxysmal nocturnal hemoglobinuria' CD, cluster of differentiation.
Figure 3.
Figure 3.
The P-STAT5 MFI in the (A) GPI+ cells and GPI− cells of PNH/AA patients and (B) GPI+ cells of normal controls with or without stimulation by G-CSF or SCF. (C) The MFI of P-STAT5 in GPI+ and GPI− cells of the bone marrow before and after G-CSF or SCF stimulation. G-CSF, granulocyte colony-stimulating factor; SCF, stem cell factor; P-STAT5, phosphorylated signal transducer and activator of transcription 5; MFI, mean fluorescence intensity; GPI, glycophosphatidylinositol; PNH, paroxysmal nocturnal hemoglobinuria; CD, cluster of differentiation.
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