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

Document Type : Original Article


1 Department of Hematology and Blood Transfusion, Students Research Center, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Immunology, Pasteur Institute of Iran, Tehran, Iran

3 Department of Medical Biotechnology, School of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran

4 Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Medical Laboratory Sciences, School of Paramedicine, Qazvin University of Medical Sciences, Qazvin, Iran


Chronic myeloid leukemia (CML) is a myeloproliferative malignancy with different stages. Aberrant epigenetic
modifications, such as DNA methylation, have been introduced as a signature for diverse cancers which also plays a
crucial role in CML pathogenesis and development. Suppressor with morphogenetic effect on genitalia (SMG1) gene
recently has been brought to the spotlight as a potent tumor suppressor gene that can be suppressed by tumors for
further 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 [new
case (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 polymerase
chain reaction (MSP) and quantitative reverse-transcription PCR, respectively.

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 gene
promoter. 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 group
was decreased (P<0.01); in the CMR group and BP-CML groups, it was increased (P<0.05). No significant correlation
between patients’ hematological features and SMG1 methylation was seen.

Our results demonstrated that aberrant methylation of SMG1 occurred in CML patients and it had a
significant association with SMG1 expression. SMG1 gene promoter showed diverse methylated status and subsequent
expression levels in different phases of CML. These findings suggested possible participation of SMG1 suppression in
the CML pathogenesis.


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