The presence of -308A TNFa is associated with anemia and thrombocytopenia in patients with Myelodysplastic Syndromes

BELLI, CAROLINA; BESTACH, YESICA; SIEZA, YAMILA; GELEMUR, MARTA; GIUNTA, MARIO; FLORES, GABRIELA; WATMAN, NORA; BENGIÓ, RAQUEL; LARRIPA, IRENE

BLOOD CELLS MOLECULES AND DISEASES

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2011 vol. 47 p. 255 - 258

1079-9796

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 (TNFa) which is a multifunctional proinflammatory cytokine. The aim of this work is to examine the presence of -308A/G TNFa 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 TNFa -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 9.9 g/dL; p=0.0206), reduced platelet counts (89,000 vs 130,000/uL; p=0.0381) and younger age (59 vs 68 years; 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 TNFa, which increases its transcription level, was associated with the MDS phenotype in our cohort of Argentine MDS patients. Also, an overexpression of TNFa 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.