Study On STAT5Phosphorylation In CD34~+CD38~-CD123~+Bone Marrow Cells Of The Patients With Myelodysplastic Syndromes

ObjectiveTo investigate the quantity of CD34+CD38-CD123+bone marrow cells and the expressions of STAT5phosphorylation in these cells of the patients with Myelodysplastic Syndromes (MDS), and then evaluate the level of activation of STAT5associated with cell proliferation in those MDS clone cells.MethodsThe bone marrow mononuclear cells(BMMNC)were extracted from36cases of MDS patients and14normal controls. The mean fluorescence intensity (MFI) of phosphorylated STAT5(P-STAT5) and total STAT5in CD34+CD38-CD123+and CD34+CD38-CD123"cells, with or without the stimulation of10U/ml EPO and expressions of CD34+CD38"CD123+, were examined by flow cytometry(FCM)ResultsThe ratios of CD34+CD38"CD123+/BMMNC in the bone marrow cells of low-risk, high-risk MDS [(0.02±0.01)%,(0.48±0.27)%] were significantly higher than that of normal control [(0.00±0.00)%, P<0.05]; The ratios of CD34+CD38-CD123+/CD34+CD38" in the bone marrow cells of low-risk, high-risk MDS [(35.23±18.85)%,(51.12±24.85)%)] were significantly higher than that of normal control [(9.06%±10.04%, P<0.01, P<0.05). Both the ratios in high-risk MDS were significantly higher than those in low-risk MDS.Without stimulation, the P-STAT5MFI in CD34+CD38-CD123+cells of low/high risk MDS patients was113.71±67.22/173.05±102.78, which was significantly higher than that of CD34+CD38-CD123-cells(58.84±27.51/68.99±50.42, P<0.01,P<0.05) and the normal controls CD34+CD38-CD123-cells (63.06±21.06,P<0.05), there was no significant difference between the CD34+CD38-CD123-cells of MDS patients and the normal control CD34+CD38-CD123-cells; With the EPO stimulation, the P-STAT5MFI in CD34+CD38"CD123+cells of low/high risk MDS patients was144.04±58.11/239.45±152.05,which was significantly higher than that of CD34+CD38"CD123-cells (68.41±25,10/64.21±23.43, P<0.01) and the normal controls CD34+CD38-CD123-cells (75.21±27.02,P<0.01),there was no significant difference between the CD34+CD38-CD123-cells of MDS patients and the normal control CD34+CD38"CD123-cells; The Increased P-STAT5MFI between the EPO stimulation and without stimulation,the CD34+CD38-CD123+cells of low/high risk MDS patients was21.805/28.855,which was significantly higher than that of CD34+CD38-CD123-cells (7.415/5.50, P<0.01, P<0.05) and the normal controls CD34+CD38-CD123-cells (6.39, P<0.05), there was no significant difference between the CD34+CD38-CD123-cells of MDS patients and the normal controls CD34+CD38-CD123-cells; There was no significant difference of P-STAT5MFI with or without EPO stimulation and the increased P-STAT5MFI between the CD34+CD38-CD123+cells of low and high risk MDS. There was no significant difference of total STAT5MFI between the CD34+CD38-CD123+cells and CD34+CD38-CD123-cells. The P-STAT5MFI in CD34+CD38-CD123+cells of high risk MDS was significantly positively correlated with the ratios of CD34+CD38-CD123+/BMMNC(r=0.454, P<0.05) and blast cells in the bone marrow(r=0.589, P<0.05) and the malignant clone burden(r=0.676, P<0.05).ConclusionIn MDS, STAT5associated with cell proliferation was activated in CD34+CD38-CD123+bone marrow cells which had more significant reactions to EPO than CD34+CD38-CD123-cells, indicating that CD34+CD38-CD123+bone marrow cells might be the real malignant MDS clone cells in MDS.