Clinical Study On Expression Of Bcl-2in Chronic Myelogenous Leukemia

Objective:Chronic myelogenous leukemia（CML）is a proliferative malignant tumor of the bone marrow.The BCR-ABL fusion gene is an important regulatory mechanism of the occurrence and development of CML,as well as a key therapeutic target.With the emergence of Tyrosine kinase inhibitors（TKI）,the overall survival rate of patients with CML has been very close to that of the healthy population.Meanwhile,some patients did die due to drug resistance and disease progression.B cell lymphoma/leukemia（BCL）-2 plays a major role in the antiapoptotic genes and one of the key genes in the occurrence and development of CML,and plays a crucial role in the occurrence of drug resistance of CML as well.Therefore,by comparing the expression levels and correlation analysis of Bcl-2 mRNA in patients with CML,the control group,and patients before and after TKI treatment,this study explores the pathogenic mechanism of Bcl-2 on CML,and provides new perspectives on prognostic factors of CML,as well as possible strategies for the treatment of drug-resistant patients with CML.Methods:Sixty patients with CML who were diagnosed and treated in Hematology Department of Northern Jiangsu People’s Hospital from January 1,2016to December 31,2020 were selected as the experimental objects,all of whom were in chronic phase.The 60 patients were divided into the following groups:1.11 patients were included in the newly diagnosed group.Their peripheral blood（PB）was collected in the initial diagnosis,3rd month,6th month and 12th month after treatment respectively.According to the treatment time,they were divided into four groups:newly diagnosed-0 group,newly diagnosed-3 group,newly diagnosed-6 group and newly diagnosed-12 group.2.follow-up groups:A total of 49 patients,all of whom received more than one year of TKI treatment,were divided into the following groups in accordance with BCR-ABL^ISlevel:（1）Follow-up Group A:BCR-ABL^IS<0.1%;（2）Follow-up Group B:0.1%<BCR-ABL^IS<10%;（3）Follow-up Group C:BCR-ABLIS>10%.At the same time,10 healthy adults without malignant neoplastic diseases got involved in the control group.Collect clinical data and PB of CML patients,PB of the control group,and q RT-PCR was utilized to figure out the relative expression level of Bcl-2 mRNA in PB of the control group and CML patients in different groups.Analyze the expression differences of BCL-2 in different groups and risk grades of CML patients,and the correlation between BCL-2 and CML.Results:1.Among the 60 CML patients,the most common clinical manifestations at onset were splenomegaly 63.33%（38/60）,fatigue 43.33%（26/60）,anemia 31.67%（19/60）,weight loss 31.67%（19/60）,splenic discomfort 30.00%（18/60）,night sweat8.33%（5/60）,and fever 6.67%（4/60）.2.Expression of Bcl-2 mRNA in CML patients and the control group:（1）The mean relative expression of Bcl-2 mRNA was1.00±0.83,5.18±3.87,1.15±1.50,1.82±2.36 and 3.33±2.89 in the control group,newly diagnosed group-0,follow-up group A,B and C,respectively.Moreover,there was a significant difference among the those groups P=0.015.Compared with the initial diagnosis group-0,the expression of Bcl-2 mRNA was found to be low in the control group（P=0.010）,follow-up group A（P=0.005）and B（P=0.011）,with statistical significance.（2）In comparison with follow-up group A,the expression of Bcl-2 mRNA was remarkably increased in the newly follow-up group C（P=0.034）,with statistical significance.The expression of Bcl-2 mRNA in the follow-up group A,B and C was respectively higher than that in the control group,but with no statistical difference（P>0.05）.（3）The relative expression of Bcl-2 mRNA in MMR group(BCR-ABL^IS<0.1%)was lower than the group that didn’t get the MMR（P=0.234）,but there was no remarkably difference between the two groups（P>0.05）.3.Both before and after treatment in patients with the quantity of the BCL-2mRNA expression:PB samples were collected from the 11 patients with CML at the time of initial diagnosis,3th month,6th month and 12th month after treatment,the average relative expression of BCL-2 mRNA was 5.18±3.87,0.93±1.71,0.62±0.28,0.39±0.57respectively,and after treatment the BCL-2 mRNA relative expression quantity was on the decline,and was much lower than those who were not been treated,relatively significant differences（P=0.0022）,with statistical difference（P<0.05）.4.The relative expression of Bcl-2 in newly diagnosed patients in different Sokal grades:the mean relative expression of Bcl-2 mRNA in low-risk group,medium-risk group and high-risk group was 2.17±1.55,4.90±1.53 and 8.65±0.55,respectively.In comparison with the low-risk group,The level of Bcl-2 mRNA was found to be high in high risk group（P=0.007）,with significant difference.The level of Bcl-2 mRNA in the medium-risk group was higher than that in the low-risk group,but with no significant difference（P>0.05）.5.Correlation between expression of Bcl-2 mRNA and CML:（1）The level of Bcl-2 mRNA was significantly correlated with the expression level of BCR-ABL（r=0.372,P=0.010）,and which was statistically significant,and was positively correlated.（2）The relative expression level of Bcl-2 mRNA was significantly correlated with the hemoglobin content in CML patients（r=-0.34,P=0.034）,and showed a negative correlation.（3）There was no significant correlation between Bcl-2 mRNA relative expressi-on and erythrocyte,white blood cell,neutrophil,eosinophilic,basophilic and platelet count in CML patients（P>0.05）.（4）There was no significant correlation between Sokal grade and Bcl-2 mRNA relative expression in newly diagnosed patients with CML r=0.588,P=0.074,（P>0.05）.（5）The relative expression of Bcl-2 in newly diagnosed patients with CML was positively correlated with spleen size,r=0.784,P=0.007.Conclusion:1.Bcl-2 gene may play a role in the occurrence and development of CML.2.The increased expression of BCL-2 mRNA may indicate the poor prognosis of CML,and provide a theoretical basis for clinical practice.