Expression Of SIRT3 In Acute Myeloid Leukemia And Its Significance

ObjectiveTo observe the dynamic changes of reactive oxygen species（ROS）,isocitrate dehydrogenase 2（IDH2）,and sirtuin 3（SIRT3）in patients with acute myeloid leukemia（AML）before and after chemotherapy,and to explore ROS,IDH2,and SIRT3 in different AML patients The difference of levels and its application value in clinical diagnosis and efficacy evaluation.MethodsBone marrow and peripheral blood samples were taken from 20 newly diagnosed AML（non-APL）patients who had not undergone chemotherapy;bone marrow and peripheral blood samples were taken from 40 AML（non-APL）patients who had undergone chemotherapy;Peripheral blood samples served as controls.After the bone marrow mononuclear cells were isolated,the cells were collected and resuspended in DCFH-DA and Mito-Tracker Green working solution,respectively,and protected from light throughout the process.After that,the stained cells were collected in a six-well plate,and an inverted fluorescence microscope was used to observe the bone marrow.The expression of ROS in mitochondria of mononuclear cells and bone marrow mononuclear cells was analyzed using image J software for mean fluorescence intensity.The expressions of IDH2 and SIRT3 in peripheral blood were determined according to the detection methods of different ELISA kits.The patients with positive AML1-ETO fusion gene were summarized,and the expression of SIRT3 in different gene expression groups was compared.The treatment efficacy,treatment course,classification of acute myeloid leukemia,and chromosomal differences in different patients were summarized,and the expression of SIRT3 in different groups was compared.ResultsThe expression of bone marrow mononuclear cells and mitochondrial ROS in the newly diagnosed group was higher than that in the control group,and the difference was statistically significant（P<0.05）.The expression levels of IDH2 in peripheral blood of the control group,the newly diagnosed group and the treated group were（11.00±4.49）,（18.95±5.02）and（14.99±5.07）μg/L respectively;the newly diagnosed group was higher than the control group,and the difference was statistically significant Scientific significance（P<0.0001）;the treatment group was lower than the newly diagnosed group,and the difference was statistically significant（P<0.05）.After 5-fold dilution of peripheral blood,the expression of SIRT3 was（937.47±155.43）,（590.65±116.19）,and（758.76±220.49）ng/L,respectively.The newly diagnosed group was lower than the control group,the difference was statistically significant（P<0.0001）;the treated group was higher than the newly diagnosed group,the difference was statistically significant（P<0.01）.In the post-treatment AML patients,there was no significant difference in the expression of SIRT3 between the fusion gene AML1-ETO positive and negative expression.According to the different therapeutic effects of patients,among the treated AML patients,the expression of SIRT3 was slightly higher in the partial remission patients,but there was no significant difference compared with the complete remission patients.In the complete remission subgroup of treated patients,according to the different treatment courses,the SIRT3 expression in patients with a longer treatment course was slightly higher than that in patients with a short treatment course,but the difference was not significant.According to the different risk levels of patients,there was no significant difference in the expression of SIRT3 in the newly diagnosed AML patients;there was no significant difference in the SIRT3 expression in the treated AML patients.According to the analysis and comparison of patients with different acute myeloid leukemia types,there was no significant difference in the expression of SIRT3 between the newly diagnosed AML patient group and the treated AML patient group.According to the comparison of different chromosomal types of patients,there was no significant difference in the expression of SIRT3 between the newly diagnosed AML patient group and the treated AML patient group.Among the treated AML patients,the MRD was 1x10^-4,the SIRT3 expression was（655.73±125.57）ng/L;the MRD was 2x10^-4,the SIRT3 expression was（710.39±157.56）ng/L;MRD For 3×10^-4 patients,their SIRT3 expression was（887.63±278.14）ng/L.Among them,there was no difference in the expression level of SIRT3 between patients with MRD of 1x10^-4 and 2x10^-4（P>0.05）.Compared with patients with MRD of 1x10^-4 and 3x10^-4,the expression level of SIRT3 was different（P<0.05）,and compared with patients with MRD of 2x10^-4 and 3x10^-4,the expression of SIRT3 was different（P<0.05）.ConclusionSIRT3 is an important protein that regulates metabolic function in the mitochondria of cells.Its expression is down-regulated in patients with acute myeloid leukemia,and the expressions of IDH2 and ROS are increased accordingly.In AML,abnormal expression of SIRT3,which affects the level of intracellular ROS,may provide a new predictor of therapeutic efficacy for patients with acute myeloid leukemia.