The Level Of Erythropoietin And Expression Of Erythropoietin Receptor In Myelodysplastic Syndrome

Background:Myelodysplastic syndrome (MDS) encompass a group of clonal hemopoietic stem/progenitor cell disorders characterized by refractory cytopenia in peripheral blood,dysplastic cellular morphology in bone marrow,and a high risk of malignant transformation to acute leukemia, Which were involved in the process of signal transduction and genes related to cell proliferation and differentiation. The abnormal of stem cell, alteration of hematopoietic microenvironment and defective immunologic mechanism may play important roles in the pathogenesy of MDS. The dysplastic erythroid and cytopenia in peripheral blood are the early characteristics in MDS patients with MDS frequently experience symptomatic anemia, and the symptoms of most MDS patients show dependence on blood transfusion and some degree of anemia, which is one of the most common clinical features in hematologic malignances and has influences the life quality and survival time seriously. The mechanism of anemia is complicated. Erythropoietin (EPO), a 30,400 dalton glycoprotein hormone, mainly regulates the proliferation and differentiation of erythrocytic progenitors. p66, encoded by EPOR, is a 66 kilodalton glycoprotein and a I type ransmembrane glycoprotein composed by 507 Amino Acid. etythropoietin and its receptor developed a dimeride, which regulated the proliferation and differentiation for erythrocytic stem cells by JAK/STAT and RAS/MAP kinase signal. erythropoietin, interleukin-3 and macrophage colony stimulating factor regulated the proliferation of burst-forming unit-erythroid,and the advanced stage was mainly regulated by erythropoietin. For the past few years, there were several researches aimed at the EPO level in MDS, but little research about the defect of EPOR. Some study have confirmed the abnormal expression of EPOR gene in MDS patients and proposed that it might be involved in the paraplasm of erythrocytic progenitors. In order to indentify the effect of EPO level and EPOR in anemia, we designed this study to determine the expression of erythropoietin receptor and erythropoietin in Myelodysplastic Syndrome and their relation with the clinical situation in MDS patients, so as to provide a theoretical basis for EPO therapy in Myelodysplastic Syndrome with anemia.Objective:This study was designed to determine the expression of erythropoietin receptor and erythropoietin in Myelodysplastic Syndrome and their correlation with the clinical situation in MDS patients, so as to provide a theoretical basis for EPO therapy in Myelodysplastic Syndrome with anemia.Methods:The EPOR in 45 MDS patients was detected using reverse transcription polymerase chain reaction (RT-PCR), and the level of serum Erythropoietin was detected by enzyme linked immunosorbent assay (ELISA) in 11 patients with refractory anemia(RA),9 patients with refractory cytopenia with multilineage(RCMD),10 patients with refractory anemia with excessive blasts-1(RAEB-1) and 15 patients with refractory anemia with excessive blasts-2(RAEB-2). The patients were divided into low-risk group(RA,RCMD) and high-risk group(RAEB-1,RAEB-2) according to the categorization of WHO.Results:EPOR was expressed in 25 of 45 MDS patients, the relative level of EPORmRNA expression had no significant difference between low-risk MDS patients(0.6862±0.3725) and control group (P>0.05). The relative level of EPOR mRNA expression in high-risk MDS patients was significantly lower than that in control group (0.4023±0.1385 vs 0.8347±0.2541)(P<0.05).The level of sEPO in low-risk MDS patients was significantly lower than that of control group (13.91±7.70) IU/L vs (20.57±9.06) IU/L (P<0.05);and the level of sEPO in high-risk MDS patients(30.68±14.08)IU/L was significantly higher (P<0.05).Conclusion:The lower sEPO might play a role in low-risk MDS patients; the expression of EPOR in high-risk patients was decreased or deletion, but the level of sEPO was significantly increased,so we suggested that the decreased expression of EPOR might cause erythroid abnormal in high-risk MDS patients, thus providing a clue for EPO therapy in Myelodysplastic Syndrome.