[Show abstract][Hide abstract] ABSTRACT: Abstract The impaired hematopoiesis in acquired aplastic anemia (AA) results from immune-mediated mechanisms. We characterized polymorphisms implicated in controlling type-1 cytokine production in 69 AA patients. Our data suggest that the studied polymorphisms are not associated with susceptibility in the overall AA population. However, the presence of the higher expressing TNF -308A allele was associated with younger age (p=0.0297), more profound neutropenia (p=0.0312), and over-represented in very severe AA patients (p=0.0168). The higher producing IFNG 12 CA-repeat allele showed a strong linkage disequilibrium with +874T allele, and was associated with lower hemoglobin level (p=0.0351). Also, the presence of at least one higher expressing variant was more frequent among responder patients to immunosuppressive treatment (p=0.0519). Our findings suggest that the presence of higher expressing variants of TNF-α and IFN-γ in AA patient's genotypes would be related to clinical parameters, disease severity and therapy outcomes.
Leukemia and Lymphoma 09/2014; 56(6):1-12. DOI:10.3109/10428194.2014.966707 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Myelodysplastic Syndromes (MDS) are a heterogeneous group of hematological diseases characterized by refractory cytopenia(s) and variable risk
of leukemic progression. Cytogenetic analysis is important in day-to-day clinical practice helping to define subgroups of MDS patients who share
similarities in the course of the disease. There are recurring aberrations affecting chromosomes 5, 7, 8, and 20. While all of them do not suggest a
therapeutic approach, their presence has been considered as a risk indicator since the original international prognostic scoring system (IPSS) was
published. The most recent cytogenetic stratifications tried to find the prognostic significance of less frequent alterations which have been longer
included in the intermediate group. Moreover, monitoring of karyotype changes is suggested to evaluate cytogenetic response to treatments and the
acquisition of new aberrations associated to an unfavorable outcome. This review focuses on different cytogenetic risk stratifications that have been
published during the past twenty years and the molecular background of the most relevant chromosomal findings.
[Show abstract][Hide abstract] 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.