Expression Levels Of Beclin1-and Atg5-mRNA And Its Clinical Significance In Acute Leukemia

Objective: To detect the expression levels of autophagy-related genesBeclin1and Atg5in bone marrow mononuclear cells (BMMNC) collectedfrom acute leukemia(AL) patients and healthy controls and to explore itsclinical significance in acute leukemia, laying the foundation for furtherinvestigating the molecular mechanism of Beclin1and Atg5in leukemiagenesis, and trying to find out the possibility of using Beclin1and Atg5astargets for the treatment of leukemia.Methods: To detect the expression level of Beclin1-and Atg5-mRNA inBMMNCs from45cases of acute myeloid leukemia (AML,15cases inlow-risk group,15cases in middle-risk group and15cases in high-risk group),30cases of acute lymphoblastic leukemia (ALL,15patients in standard riskgroup,15cases in high-risk group) and15cases of healthy controls byquantitative RT-PCR. Pearson correlation analysis was performed to evaluatethe correlations coefficient between the expresson level of these two indicatorsin leukemia patients, P value less than0.05was considered as statisticallysignificant.Results:1Expression level of Beclin1mRNA by RT-PCR detectionThe expression level of Beclin1in healthy control group was1.2264±.0582, and was1.0847±0.0765,0.8352±0.0411and0.7656±0.0464inacute myeloid leukemia low-risk group, middle-risk group and high-risk group,respectively(P <0.01). And in acute lymphoblastic leukemia, the expressionlevels of Beclin1in standard risk group and high-risk group was11.0577±0.0676and1.8099±0.0588respectively. The difference in Beclin1expressionlevel between the different groups was statistically significant (P <0.01).2Expression level of Atg5mRNA by RT-PCR detection The expression level of Atg5mRNA was0.6353±0.0474in the controlgroup, and was0.5410±0.0355,0.4592±0.0410and0.3610±0.0480in lowrisk AML group, middle-risk AML group, high-risk AML group respectively.However the expression level of Atg5mRNA was6.3728±0.0490and0.6211±0.0343in standard risk ALL group and the high risk ALL group. Thedifference in Atg5expression level between the high risk ALL group andhealthy control group was not statistically significant(P=0.37>0.05),but thedifference between other groups was statistically significant(P<0.01).3The relationship between the expression level of Beclin1-and Atg5-mRNAThe expression level of Beclin1mRNA and Atg5mRNA in healthy controlgroup, acute myeloid leukemia group and in acute lymphoblastic leukemiagroup was positive correlated, the Pearson correction coefficient was0.97,0.84and0.89, respectively (P <0.01), which was also statistically significant.Conclusions：1Autophagy-related genes Beclin1and Atg5expressed both in healthy controlgroup and in leukemic patients, suggesting that autophagy commonly exist innormal cells and pathological cells. However, the expression level of bothgenes was different in different cell types, indicating that autophagy may playdifferent roles in different cell types and in the development process ofleukemia.2In acute myeloid leukemia patients, the expression level of Beclin1wasstatistically significant lower than that in healthy control group. In other words,Beclin1in acute myeloid leukemia expressed at low level, and its expressionlevel was decreased futher with the increased leukemia risk levels. In high-riskALL group and standard-risk ALL group, the expression level of Beclin1washigher than that in healty control group. Its expression level was alsodecreased futher with the increased leukemia risk levels, but still higher thanthe expression level in healthy control group.3In acute myeloid leukemia, the expression level of Atg5was statisticallysignificant lower than that in healthy control group, and with the increase inleukemia risk levels the expression level of Atg5became lower. In acute lymphoblastic leukemia, the expression level of Atg5in standard risk group ishigher than that in healthy control group, and the difference is statisticallysignificant (P <0.01). But the expression level of Atg5in high-risk group andthat in healthy control group was not significant difference (P=0.37>0.01).Asthe same, the expression level of Atg5in ALL groups was decreasedsignificantly with the increased leukemia risk levels.4A positive correlation was found between the expression levels ofautophy-related gene Beclin1mRNA and Atg5mRNA in healthy control group,acute myeloid leukemia group and acute lymphoblastic leukemia group,indicating that Beclin1and Atg5mRNA might play important roles inregulating autophagy. And the aberrant expression of Beclin1and Atg5mRNAregulate the different aspects of the formation and maturation process ofautophagy, and may involved the occurrence, development, relapse anddrug-resistant of leukemia.