Correlation Of Minimal Residual Disease And Multidrug Resistance Genes Expression In Acute Myeloid Leukemia

Objective Relapse remained an obstacle to the successful treatment of acute myeloid leukemia(AML).The source of these relapses was the persistence of minimal residual disease(MRD).The introduction of methods for MRD detection had revolutionized monitoring of treatment response in acute leukemia.Multi-parameter flow cytometry(MFC)was widely used for MRD detection.MRD reflected the response of chemotherapy,which related to sensitivity of chemotherapy and influenced by multidrug resistance.The major mechanism of multidrug resistance was upregulation of membrane-resident transporters that efflux chemotherapeutic drugs from leukemia cells.ABCB1?ABCC1?ABCC4 and ABCG2 were the most important multidrug resistance transporters.The aim of this study was to explore the correlation of MRD after chemotherapy and ABC genes expression in de novo AML by detecting ABC genes' espression at diagnose and MRD level following up,which could improve current risk stratification approaches by prediction of relapse and might facilitate adaptation of postremission therapy for patients at high risk of relapse.Methods 52 de novo AML bone marrow samples were used to detect the mRNA expression of ABCB1,ABCC1,ABCC4 and ABCG2 by real-time PCR at diagnosis.22 peripheral blood samples from normal people were detected as control group simultaneously.Furthermore,15 of the patients' marrow and other 6 denotes' marrow without abnormal were used to detect the protein expression of ABCB1,ABCC and ABCG2 by flow cytometry(FCM).All AML patients were treated by standard chemotherapy strategy.Meanwhile,we followed up these patients to monitor MRD with MFC at the points of finishing the first induction cause as well as the third,the sixth and the ninth month after chemotherapy.Results 1.The mRNA expression of ABCB1,ABCC1,ABCC4 and ABCG2 in AML patients and normal people were detected by real-time PCR.Four ABC genes expressed higher level in AML patients than in normal people,while the statistical difference only presented at ABCC1(P<0.05)and ABCG2(P<0.01).2.The protein expression of ABCB1,ABCC1 and ABCG2 in AML patients and control group were detected by FCM,the results suggested that ABCB1 protein expressed higher level in AML patients than in control group(P<0.05).Differences between AML patients and control group of ABCC1 and ABCG2 were not statistically.3.The expression of the 4 ABC transporters among three MRD levels detected after induction cause are correlated significantly with ABCB1(P<0.01),ABCC1(P<0.01),ABCC4(P<0.05)and ABCG2(P<0.05).4.After nine months follow-up,the patients whose MRD turned into positive again were detected a high ABC transports expression level,comparing with those MRD remained negative for nine months,which was of a statistically significance for P<0.01.Conclusions 1.ABCB1,ABCC1,ABCC4 and ABCG2 mRNA expression levels of AML patients were higher than the levels of normal people,while statistical differences were only showed in ABCC1 and ABCG2.2.ABCB1 protein expressed higher level in AML patients than in control group.Differences between AML patients and control group of ABCC1 and ABCG2 were not statistically.3.There proved a positive correlation of MRD and ABC transporters level in AML and showed a value of ABC transporters detection at diagnose which might contribute to evaluating prognosis,predicting relapse and guiding treatments.From the above,if a high level of ABC genes expression at diagnose,there might be warn unfavorable prognosis and the possibility of relapse,which of a great need to regular the therapy strategy.