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

Int J Lab Hematol. 2015 Apr;37(2):265-71. doi: 10.1111/ijlh.12283. Epub 2014 Aug 13.

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: India; SOCS-1; methylation; myelodysplastic syndromes; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Chromosome Aberrations
  • DNA Methylation*
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / blood
  • Myelodysplastic Syndromes / diagnosis*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Prognosis
  • Promoter Regions, Genetic*
  • Severity of Illness Index
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Young Adult

Substances

  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins