Aberrant DNA Methylation Status and mRNA Expression Level of SMG1 Gene in Chronic Myeloid Leukemia: A Case-Control Study

Abstract

Objective Chronic myeloid leukemia (CML) is a myeloproliferative malignancy with different stages. Aberrant epigeneticmodifications, such as DNA methylation, have been introduced as a signature for diverse cancers which also plays acrucial role in CML pathogenesis and development. Suppressor with morphogenetic effect on genitalia (SMG1) generecently has been brought to the spotlight as a potent tumor suppressor gene that can be suppressed by tumors forfurther progress. The present study aims to investigate SMG1 status in CML patients. Materials and Methods In this case-control study, peripheral blood from 30 patients with different phases of CML [newcase (N)=10, complete molecular remission (CMR)=10, blastic phase (BP)=10] and 10 healthy subjects were collected.Methylation status and expression level of SMG1 gene promoter was assessed by methylation-specific polymerasechain reaction (MSP) and quantitative reverse-transcription PCR, respectively. Results MSP results of SMG1 gene promotor in the new case group were methylated (60% methylated, 30%hemimethylated and 10% unmethylated). All CMR and control group patients were unmethylated in the SMG1 genepromoter. In the BP group, methylated SMG1 promoter was seen (50% of patients had a methylated status and 50%had hemimethylated status). In comparison with the healthy subjects, expression level of SMG1 in the new case groupwas decreased (P<0.01); in the CMR group and BP-CML groups, it was increased (P<0.05). No significant correlationbetween patients’ hematological features and SMG1 methylation was seen. Conclusion Our results demonstrated that aberrant methylation of SMG1 occurred in CML patients and it had asignificant association with SMG1 expression. SMG1 gene promoter showed diverse methylated status and subsequentexpression levels in different phases of CML. These findings suggested possible participation of SMG1 suppression inthe CML pathogenesis.

Keywords

• chronic myeloid leukemia
• dna methylation
• gene expression
• smg1