The Role Of Environmental Risk Factors,UPR And Autophagy In Occurrence Of CML Of Chinese Han Adults

Objective:CML accounts for about 15%of adult leukemia,caused by both environmental exposure factors and genetic factors.But the specific etilogy is not fully understood.Most of white blood cells of leukemia patients are immature cells.UPR and autophagy play an important role on the survival,death and maturation of cells.The purpose of the study is to explore the environmental risk factors,the expression of UPR,apoptosis,cell cycle and autophagy gene effect on adult onset of CML,seeking for possible molecular markers of CML for its treatment.Methods:A hospital-based matched case-control study was conducted,including 122 adult CML-CP and 122 cancer-free controls to explore environmental risk factors as well as the expression of UPR,autophagy,apoptosis and cell cycle related genes,detected by real-time quantitative PCR.Furthermore,the effects of environmental risk factors on the expression of UPR and other related genes were discussed.Results:?Univariate analysis showed that the difference between CML group and normal controls including smoking,benzene exposure,living around road,home decoration history,living around chemical plant and high voltage cable or transmitter was statistically significant(P<0.05).While multivariate analysis showed that exposure of benzene,home decoration history,living around to the road,chemical plant and high voltage cable or transmitter were statistically significant(P<0.05).?The up-regulated genes including UPR genes GRP78,PERK?eIF2a?IRE1ATF4,XBP1,SXBP1,anti-cell death genes AKT1 and NF-?B;JAK2,BCR-ABL1 and ERK were observed(P><0.05).While the down-regulated genes including cell-death genes JNK1 and CASPASE12,Autophagy-related genes ULK1,mTOR?BECLIN1?ATG12?VPS34,Cell cycle gene CCNE1 and CD44 were observed(P<0.05).?The effect of benzene exposure of CML to down-regulatation of VPS34 was statistically significant(P<0.05).While the effect of home decoration history to expression of NF-?B and ATG12 was statistically significant(P<0.05).The effect of living around chemical plants to expression of eIF2a,mTOR,ULK1 and ATG12 was statistically significant(P<0.05).Conclusions:?The risk of benzene exposure,home decoration history and living environment close to the road,chemical plant and high voltage cable or transmitter for Han adults CML was increased.?UPR and autophagy may play a crucial role on occurrence of CML.?The up-regulation of BCR-ABLl is associated with CML.?Benzene exposure may be associated with down-regulation of gene VPS34 in CML;While living around chemical plant may be associated with down-regulation of gene ULK1 and ATG12.