The Role Of Hippo Signaling Pathway During Occurrence And After IM Treatment Of CML In Chinese Han Adults

Objective:To investigate the effect of environmental factors on Hippo signaling pathway in the patients with Chronic Myeloid Leukemia(CML)during the onset of chronic disease,the role of Imatimib(IM)on the pathway,and then to find the function of Hippo signaling pathway during occurrence and after IM treatment of CML,and provide laboratory reference indicators for CML treatment and prognosis.Methods:A group matched case-control study was firstly used to the action of environmental factors on CML chronic phase(CP-CML)patients:a simple random sampling was used to find the patient and the control groups.All patients were Chinese Han adults,and diagnosed as CP-CML for the first time in a hospital of Suzhou from August 2015 to June 2017.All these CML patients were excluded other tumor history and blood system disease,and confirmed as BCR-ABL fusion gene positive.The control group were healthy Chinese Han adults who took part in the medical examination at the same time and matched the cases according to the sex and age(±5years)and excluded people with blood system diseases and tumor history.With our questionnaire,the"one-to-one" queries were carried in the patient and the control groups.The survey contents included general demographic information,the histories of smoking,drinking,paint exposured,home decoration,exposured to radioactive substances and hair dyeing.A total of 96 valid questionnaires were collected from the patient group and the control group.Then,the influence of environmental factors on CML in Han adults was analyzed by ?2 test,and the possible risk factors of CML in them was analyzed by Logistic regression.Simultaneously,96 cases of anticoagulant venous blood(each about 5ml)were collected from each group.And then,by the real-time fluorescence quantitative PCR,the expression of the core genes and the regulation genes in the Hippo pathway were measured,and the t-test method was used to analyze the correlation between the environmental factors and the Hippo signaling pathway during occurrence of CML in Han adults.At last,a cohort study was carried on the follow-up studies:after the patients leaved the environment that maight induce CML and were treated with IM for six months,we had visited the control group and the patient group,and collected 90 cases of anticoagulant venous blood(each about 5ml)were from each group.And then the mRNA abundance of the core genes and regulatory genes of the Hippo pathway was detected by the real-time fluorescence quantitative PCR,and the influence of IM on the Hippo signaling pathway in CP-CML patients was analyzed by t-test statistics method.Results:? The history of hair dyeing and paint exposure were associated with the occurrence of CML(P<0.05),and the multivariate analysis showed that this two variables maight be the risk factors of CML(P<0.05).?Compared with the CML patients without hair dye,the expression of CD44 and YAP increased in the hair-dyed CML patients(P<0.05);compared with the CML patients without radiation exposure,the expression of CD44 increased in the CML patients with that(P<0.05).?Compared with the control group,the expression of MST1/2,LATS1/2,FAT4,KIBRA,FRMD6,RASSF1A,ATM,RHOA,PTPN14 and AMOT decreased in the CML patients(P<0.05),while the expression of YAP,CD44 and KRAS increased significantly(P<0.05).There was no difference in other gene expression(P>0.05).?Most of the patients were in a state of remission after been released from the risk environment and treated by IM.Compared with the control group,the expression of MST1/2,LAT1/2,FAT4,KIBRA,FRMD6,RASSF1A,ATM,RHOA and AMOT became normal after IM treatment(P>0.05),while YAP,CD44 and KRAS were still significantly increased(P<0.05),and PTPN14 was still dramatically decreased too(P<0.05).? After the patients were removed from the dangerous environment and treated by IM for 6 months,the expression of MST1/2,LATS1/2,FAT4,KIBRA,RHOA,PTPN14 and AMOT was higher than before(P<0.05),while YAP and CD44 showed lower expression(P<0.05),and there was no difference in the other genes(P>0.05).Conclusions:? With the exposure to the paint and the dye-hair,the risk of CML maybe increased in Han Adults.?The dye-hair and the radiation probably increased the expression of YAP and CD44 in CML.?Signal transduction of Hippo pathway maybe suppressed during occurrence of CML,and IM maight not only reactivate the Hippo pathway but also caused CML patients to remission.The up-regulated YAP and CD44 maight indicate that CML patients had not yet recovered.