Correlation Between SOCS-3 Gene Expression And Its Methylation With Acute Lymphoblastic Leukemia In Children

Background Acute leukemia is a malignant clonogenic disease,it is also one of the most common malignant tumors in children.It accounts for about 25% in all the malignant tumors of children.The annual incidence rate in children is about 3-4/100000,and it is increasing year by year.It has seriously threatened the life and the health of children in China.Acute lymphoblastic leukemia(ALL)is a very common subtype of AL.In recent years,with the progress and the emergence of some new treatments,the 5 year disease free survival rate of ALL is close to 80%.However,there is still about 20% percent patients fail to achieve complete remission or relapsed after remission.The inhibitory factor of cytokine signal transduction is a new type in immunosuppressant family,which plays an important role in the regulation of specific immunity and inherent immunity.SOCS-3 is one of the members of the SOCS family.Under normal circumstances,SOCS-3 is low expressed in cells and tissues,and its transcription and activation are regulated by JAK/STATs pathway.However,recent studies have found that the abnormal methylation of SOCS gene is related to the pathogenesis of many tumors,and has a certain relationship with its development,such as hepatocellular carcinoma,prostate cancer,myelodysplastic syndrome,multiple myeloma and so on.However,at present,the relationship between the methylation of SOCS gene and the relationship between ALL is less.In this study,the methylation of the SOCS-3 gene in theblood specimens of ALL patients is measured by real-time quantitative RT-PCR,and the correlation with the prognosis of ALL is also analyzedObjective To investigate the correlation between SOCS-3 gene expression andits methylation with acute lymphocytic leukemia in childhood.Methods This study included 40 patients with newly diagnosed ALL who were admitted to our hospital from October,2015 to September,2017.All the patients were diagnosed with the recommendations of the diagnosis and treatment of children’s acute lymphoblastic leukemia in 2014(Fourth Revision).Blood samples were collected from newly diagnosed and untreated ALL patients.There were 20 boys and 20 girls,aged 8 months to 14 years(median 5.8 years).All the patients were given regular chemotherapy according to CCCG-ALL-2015 plan.The blood specimens from the control group were collected from 10 patients with controls,including 5 boys and 5 girls.None of these patients had any clinical evidence of tumor disease.The total RNA was extracted and the expression level of SOCS-3 gene was detected by real-time fluorescence quantitative RT-PCR.Methylation primers and non methylation primers were designed respectively.Methylation specific polymerase chain reaction was used to detect the methylation status of SOCS-3 Cp G island in two groups of blood specimens.Finally,the relationship between the methylation status of SOCS-3 gene and clinical data in ALL patients was statistically analyzed.Results1)The expression of SOCS-3 m RNA in the peripheral blood of the ALL group and the healthy control group: the relative expression of SOCS-3 gene in the early diagnosis group and the relapse group was significantly lower than that in the CR group and the healthy control group,and the difference was statistically significant.There was no significant difference between the CR group and the healthy control group.2)The expression level of SOCS-3 gene methylation in peripheral blood of the ALL group and the control group: the level of relative expression of SOCS-3 methylation gene in the primary,recurrent and CR groups was significantly lower than that in the healthy control group,and the difference was statistically significant.There was no significant difference between the first diagnosis group and the relapse group.3)The relationship between the methylation status of SOCS-3 gene and the clinical data of ALL patients: the methylation of the SOCS-3 gene has no significant correlation with the patient’s age,sex,and the classification of ALL(T-ALL or B-ALL).4)The relationship between SOCS-3 gene expression and methylation expression in ALL group: the relative expression of SOCS-3 gene in ALL methylation group(0.371 + 0.227)was significantly lower than that of non methylation group(1.030 + 0.402),and the difference was statistically significant.Conclusion In this study,we discussed the relationship between SOCS-3 and ALL from the expression and methylation level of SOCS-3 in ALL.The methylation of Cp G island of SOCS-3 gene leads to SOCS-3 gene silencing and expression loss or deletion,which is probably related to the occurrence and development of ALL.Therefore,the methylation of the SOCS-3 gene is closely related to the occurrence and development of ALL,and may be one of the molecular markers for the early diagnosis of ALL patients.In addition,gene inactivation caused by methylation can be reversed,so it is possible to control the occurrence and progress of ALL by removing methylation of the SOCS-3 gene by demethylation and inducing the expression of the SOCS-3 gene.The demethylation of SOCS gene in ALL patients may be valuable for the control of ALL.However,because SOCS is involved in the transmission of numerous cell signals,the process of action also involves many complex pathways.Therefore,more studies are needed to further confirm the exact role and mechanism of SOCS in ALL.