| Objectives:Survivin is a member of inhibitor of apoptosis proteins(IAP),which inhibits apoptosis by directly banding with cysteine protease-3(caspase-3) and cysteine protease (caspase-7). Survivin is strictly expressed in G2/M phase during mitosis, and it is required for apoptosis inhibition,which may provide a selective cytoprotective mechanism at cell division,thus to promote cell division and proliferation.Survivin is expressed in many tumors,and its high expression associates with poor prognosis.Smac(second mitochodria-derived activator of cas- pase) is a proapoptosis protein releasing from mitochondrion, which induces cell apoptosis by relieving the inhibition of IAP.Our study intends to investigate the expression of Survivin and Smac in leukemia and the prognostic significance in acute leukemia(AL) .Methods:The expression of Survivin and Smac mRNA were measured in 119 adult leukemia patients(including 78 de novo acute leukemia patients,7 replased patients,14 chronic granulocytic leukemia patients in chronic phase and 20 complete remission patients),15 samples of normal controls(NC) and K562,NB4,KG-1α,HL-60 cell lines by semi-quantity reverse transcription polymers chain reaction(RT-PCR).In the meaning time,we measured the cell cycle distribution in de novo AL with FCM.Then analyzed the relationship between Survivin and proliferation.Results:1 Using RT-PCR analysis of the expression of Survivin and Smac mRNA1.1 The expression of Survivin mRNA in de novo AL patients (mean 0.525,positive rate 73.1%) is significantly higher than NC(mean 0.101, positive rate 26.7%),there is statistical difference between them,P=0.026;There is no difference between AML(mean 0.475,positive rate 69.8%) and ALL(mean 0.733,positive rate 86.7%),P=0.078;In relapse group,Survivin mRNA(mean 0.935, positive rate 100%) is higher than NC(P=0.000),as well higher than AL(P=0.026);there is no difference between CR-patients (mean 0.280,positive rate 35%) and NC,but AL group is higher than CR group,P=0.023.1.2 The expression of Smac mRNA in AL(0.554,69.2%) is higher than NC(0.031,6.7%),P=0.000;there is no difference of expression of Smac between AML and ALL(P=0.22).In 7 case of replased patients,6 cases are positive.The mean level is 0.583,which is higher than NC,but it is no difference from AL(P=0.158).The mean level of Smac mRNA in CR-patients is 0.244,and positive ratio is 30%,with no difference compared with NC(P=0.07).1.3 50% of CML-CP patients have Survivin mRNA expres- sion,with the mean level 0.279,which is higer than NC,but there is no statistical difference(P=0.105).The expression of Smac mRNA in CML-CP is higher than that of NC,but no difference(P=0.091),too.In 5 case of blastic phase(BP) patients, the expression of Survivin and Smac mRNA are both higher than those in NC(P=0.008,P=0.012).But there is no difference between BP and CP(P=0.134,P=0.379). 1.4 The level of Survivin (and Smac) mRNA is unequal in FAB typing,but there is no statistical difference(P>0.05).1.5 In the 4 leukemia cell lines,Survivin and Smac mRNA both express high level.2 A positive correlation is observed between Survivin and Smac mRNA (r=0.645,P=0.000).3 In AL,the cases with high level of Survivin (or Smac) have higher proliferation index(PI=9.682,PI=9.592)than those not (PI=6.899,PI=6.428),with significant difference(P=0.015,P= 0.020).4 We have an effect evaluation on 61 cases of patients(6 died in early period, 11 were untreated).The remission rate is higher in Sur- patients (13/14,93.3%) than that in Sur+ patients (28/46,60.9%),χ2=4.148,P=0.042.A similar result is obtained in Smac, χ2=5.472,P=0.019.In Sur-Smac- double negative group, the CR rate is significantly higher than that in Sur+Smac+ double positive group(P=0.01).In AML,the patients with high level of Survivin or Smac have a lower CR rate,but in ALL,there is no difference between two groups.The CR rate in Sur+,Smac+ are lower than double negative group(P<0.05).In relapse group, only one of them is remitted by chemical medicine,who is positive with...
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