Suppressor Of Cytokine Signaling1Hypermethylation In Multiple Myeloma

To investigate the promoter hypermethylation and transcription of suppressor of cytokine signaling1gene, and to explore their relationship with etiology of multiple myeloma. It is possible and helpful to search some new theoretical basis about the molecular mechanism, therapy and prognosis of MM. It also may be prevented some experimental data to biological makers, targeting therapies and genome methylation of MM.Methods:54multiple myeloma patients (27newly-diagnosed,35men,19women, ages range38to78, median age64), who presented at First and Second Affiliated Hospital of Kunming Medical University between January2009to June2011, were enrolled in the study. The control group includes40patients with nutrient deficiencies anemia and immune thrombocytopenia (15men,25women, ages range19to68, median age42). All bone marrow aspirates were investigated by MSP and RT-qPCR, and the MSP products were confirmed by auto DNA sequencing. The correlations of results were analyzed by SPSS17.0(Statistical Product and Service Solutions).Result:1.The results of MSP:①16.67%(9/54) myeloma samples showed SOCS1hypermethylation in the3'promoter region. None of positive result (0.00%,0/40) is detected in the control group. There is significant difference between the two group (P<0.05);②In the5'promoter site of SOCS1, hypermethylation were not detected in MM patients BM (0/54) and control group samples (0/40);③These factors (gender, age, stage, grouping, diagnosis and immunoglobulin) are analyzed with the methylation. However, we found that the methylation of SOCS13'promoter region is not related to these factors. 2. DNA sequencing results:The methylation can be detected; generally, there will be19sites methylated in the3'promoter region and22sites in5'promoter in SOCS1gene. However, methylated sites differ in different samples and we need more samples to evaluate this phenomenon.3.RT-qPCR results:relative expression of SOCS1mRNA, median±quartile of myeloma patients samples is12.39±18.32Fold, the control group is13.51±26.38Fold (mean±std); methylated group is17.00±16.52Fold (mean±std), and unmethylated group is16.45±17.97Fold Fold; newly-diagnosed sample is11.47±23.15Fold, treated sample is18.93±17.59Fold. Unfortunately, all of three group data have no correlations (P>0.05).Conclusion:1. In the survey, hypermethylation of SOCS13'promote has confirmed in54MM patients and differed significantly between MM and the control group and the sequencing results have confirmed the methylation of SOCS1and multiple sites are methylated in our study. But3'promoter region has no correlation with factors of gender, age, stage, newly-diagnosed and immunoglobulin. These data indicate that methylation of SOCS1might have an important role in pathogenesis of MM.2. In the test, there are no correlation of expression of SOCS1mRNA between MM patients and the control group. Moreover, between methylated MM group and unmethylated group, or new-diagnosed patients and treated patients are still no significantly differences. However, it is hard to deny its biological siganificance. Therefore, the expression of SOCS1might be affected by number of specimen, treatment and some immunomodulatory cytokines.