The presence of -308A TNFα is associated with anemia and thrombocytopenia in patients with myelodysplastic syndromes

Blood Cells Mol Dis. 2011 Dec 15;47(4):255-8. doi: 10.1016/j.bcmd.2011.09.003. Epub 2011 Oct 7.

Abstract

Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases characterized by refractory cytopenia(s). MDS patients show increased levels of tumor necrosis factor alpha (TNFα) which is a multifunctional proinflammatory cytokine. The aim of this work is to examine the presence of -308A/G TNFα variants and to analyze whether it is associated with clinical parameters in a cohort of 101 Argentinean de novo MDS patients. The A/A+A/G genotype at TNFα -308 was overrepresented 2-fold in our population (p=0.0499, odds ratio-OR: 2.107) and these differences were more evident in RA-FAB subtype (p=0.0424, OR: 2.502). The presence of the high expressing -308A allele was associated with lower hemoglobin level (8.3 vs 9.9g/dL; p=0.0206), reduced platelet counts (89,000 vs 130,000/μL; p=0.0381) and younger age (59 vs 68years; p=0.0122) at diagnosis. Also, these patients showed 3.8-fold higher risk of transfusion requirement (76% vs 46%, p=0.0105) during the follow up. In conclusion, the presence of an inherited -308A TNFα, which increases its transcription level, was associated with the MDS phenotype in our cohort of Argentine MDS patients. Also, an overexpression of TNFα may promote an underlying proinflammatory state that cooperates with intrinsic defects within MDS progenitors to increase the severity of certain phenotypic features of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Anemia / complications*
  • Anemia / genetics*
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / complications*
  • Myelodysplastic Syndromes / genetics*
  • Polymorphism, Single Nucleotide
  • Thrombocytopenia / complications*
  • Thrombocytopenia / genetics*
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha