Prognostic relevance of aberrant SOCS-1 gene promoter methylation in myelodysplastic syndromes patients.

Abstract

The inactivation of suppressor of cytokine signaling SOCS-1, a negative regulator of cytokine pathways, by hypermethylation was shown in hematological malignancies including Myelsplastic Syndromes. So far, its prognostic relevance in myelodysplastic syndromes (MDS) patients has not been understood. Methylation status of SOCS-1 gene was analyzed in series of 100 patients using methylation-specific PCR (MS-PCR) and correlated with disease severity, progression, and survival by comparing prognostic factors such as hematological, clinical, and cytogenetics. Of the total of 100 MDS patients analyzed, methylation of SOCS1 gene was found in 53% patients. Also, the frequency of patients with poor and intermediate cytogenetics was observed significantly high in methylated group (P < 0.001). Moreover, the patients with methylated SOCS-1 gene had significantly more frequent disease progression as compared to the patients with unmethylated SOCS-1 gene (P < 0.006). Both progression-free survival and median overall survival were significantly shorter in patients with methylated SOCS-1 gene when compared to the patients with unmethylated SOCS-1 gene (P = 0.006 & P = 0.001, respectively). This study for the first time showed that the mathylation of SOCS-1 gene plays an important role in the disease progression and is associated with poor survival especially among the high-risk patients. This may be due to high association between SOCS1 methylation and higher risk subtypes of MDS (such as RAEB) in this study.