Expression And Clinical Significance Of XIAP, Smac, HtrA2 And XAF1 In Leukemia

Objectives:XIAP is a potent member of inhibitor of apoptosis proteins(IAP)family,which inhibits apoptosis by directly bind and inhibit caspase-3 ,caspase-7 and caspase-9. XIAP is widely expressed in normal tissues. The expression and significance of XIAP in leukemia remains to be elucidated. Smac and HtrA2 are two mitochondrial proteins,which,following apoptotic insult, translocate to the cytosol, where they interact with XIAP and neutralize the antiapoptotic effect of XIAP and sensitize cells to apoptosis. The expression and significance of Smac and HtrA2 in leukemia is not well defined.XAF1 is a nuclear protein, which directly interacts with endogenious XIAP and results in XIAP sequestration in nuclear inclusions. This study is intended to investigate the expression of XIAP,Smac,HtrA2 and XAF1 in leukemia. Methods: The expression of XIAP,Smac,HtrA2 and XAF1 mRNA were detected by semi-quantitative reverse transtription polymerase reaction(RT-PCR) in 133 cases of adult leukemia patients(comprise of 87 newly diagnosed acute leukemia patients,6 relapsed patients,11 patients in chronic myeloid leukemia chronic phase,6 patients in CML-blastic phase,and 23 patients in remission) and K562,NB4,KG-1a,HL-60 cell lines.17samples of normal persons as controls. Results To detect expression of XIAP,Smac,HtrA2 and XAF1 mRNA by RT-PCR. 1.1 XIAP mRNA was detected in all samples in variable levels. The level of XIAP mRNA in newly diagnosed acute leukemia(AL) patients is higher than that of healthy controls(0.990±0.337 versus 0.395±0.148),P<0.001.The level of XIAP mRNA in acute lymphocytic leukemia(ALL)(1.040±0.342) is higher than that of acute myelogenous leukemia(AML)( 0.971±0.343) and the difference has no statistical significance,P>0.05.The level of relapsed patients ( 1.276±0.309) is higher than that of newly diagnosed AL patients,P<0.05.The level of patients in remission( 0.655±0.219) is still higher than HC group,P<0.05. 1.2 The positivity of Smac mRNA in newly diagnosed AL patients is 65.52%.The level of AL is higher than HC group(0.449 versus 0.061, P<0.001.The difference of Smac level in AML and ALL has no stastifical significance(0.422 versus 0.521, P>0.05).The level of Smac in relapsed patients is higher than that of HC group,P<0.01. The difference between relapsed patients and AL has no statistical significance ,P>0.05.The level of Smac in remission patients is still higher than that of HC group ,P<0.005 . 1.3 HtrA2 mRNA was detected in all samples in variable levels. The level of HtrA2 mRNA in newly diagnosed AL patients is higher than that of healthy controls(1.043 versus 0.788),P<0.001.The level of HtrA2 mRNA in ALL is higher than that of AML and the difference has no statistical significance,P>0.05.The difference of level between patients in remission and HC group has no statistical significance,P>0.05. The difference between relapsed patients and AL group has no stastistical significance ,P>0.05. 1.4 XAF1 mRNA was detected in all samples of healthy controls(0.964±0.387). The expression of XAF1 mRNA in newly diagnosed AL group(56.32%,0.246) is lower than that of HC group,P<0.001.There is no difference of expression between AML and ALL,P>0.05.The mean level of XAF1 mRNA in remission patients is 0.541 with a positivity of 78.3%,and still lesser than HC group,P<0.001. 1.5 XIAP mRNA was detected in all samples of chronic myeloid leukemia patients. The level of XIAP in CML-CP is higher than that of HC group(0.637 versus 0.395),P<0.05.The expression of XIAP in CML-BC in higher than that of CML-CP,P<0.05. The level of Smac in CML-CP is higher than that of HC group( P<0.05 ).The difference between CML-CP and CML-BC has no statistical significance(P>0.05). HtrA2 mRNA was detected in all samples of CML. The difference between CML-CP and HC group has no statistical significance(P>0.05). The level of HtrA2 in CML-BC is higher than that of healthy controls(P<0.05). 1.6 In FAB classification, the difference of level of XIAP,Smac,HtrA2 and XAF1in M2,M3,M4,M5 and L2 have nostatistical significance(P>0.05 for...