Bengio R.M.,Institute Investigaciones Hematolgicas |
Riva M.E.,Hospital San Martn |
Moiraghi B.,Hospital Ramos Mejia |
Lanari E.,Hospital J. R. Vidal |
And 7 more authors.
Leukemia and Lymphoma | Year: 2011
In imatinib-treated patients with chronic myeloid leukemia (CML), BCRABL mutations are the most common mechanism of resistance. Here we report the first multicenter Argentinean study investigating mutations in those patients with CML who fail or lose response to imatinib, with or without previous interferon treatment. Point mutations were detected in 36 of 154 patients by direct sequencing. In our series, the single most common mutations were G250E, E255K/V, and M351T. The presence of mutations correlated significantly with accelerated phase, lack of molecular response, and lower cytogenetic and hematological responses. While overall survival did not differ between patients with or without mutations, the probability of progression was higher in patients with mutations. Cases with non-P-loop mutations showed a significantly better overall survival from diagnosis. Multivariate analysis showed that the most significant variables related to the development of mutations were accelerated phase, duration of imatinib treatment, and time delay to starting imatinib. Our results demonstrated that mutation frequency increased with the progression of disease, and suggest that imatinib treatment should be started early. © 2011 Informa UK, Ltd. Source
Belli C.B.,Institute Investigaciones Hematolgicas |
Bestach Y.,Institute Investigaciones Hematolgicas |
Sieza Y.,Servicio de Hematologa |
Gelemur M.,Servicio de Hematologa |
And 5 more authors.
Blood Cells, Molecules, and Diseases | Year: 2011
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 (TNF) which is a multifunctional proinflammatory cytokine. The aim of this work is to examine the presence of -308A/G TNF 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 TNF-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/L; 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 TNF, which increases its transcription level, was associated with the MDS phenotype in our cohort of Argentine MDS patients. Also, an overexpression of TNF 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. © 2011 Elsevier Inc. Source