Profile of oxidative stress in patients with chronic myeloid leukemia

A Leucemia mielÃide crÃnica (LMC) à caracterizada pela expansÃo clonal de cÃlulas progenitoras hematopoÃticas, resultante da translocaÃÃo (9:22). O oncogene de fusÃo BCR-ABL, no cromossomo Ph, à transcrito e traduzido numa proteÃna de fusÃo BCR/ABL. A tirosina quinase (TK) ABL na proteÃna de fusÃo à constitutivamente ativada sendo necessÃria para os eventos leucemogÃnicos iniciais da LMC e sua atividade induz a produÃÃo de espÃcies reativas de oxigÃnio (EROs). De particular relevÃncia para LMC à o fato de que um aumento de EROs pode ter consequÃncias, facilitando a instabilidade genÃmica podendo contribuir para a progressÃo da doenÃa. O objetivo do estudo foi determinar o perfil oxidativo em pacientes com LMC, em acompanhamento ambulatorial no Hospital UniversitÃrio Walter CantÃdio (HUWC). Trata-se de um estudo transversal constituÃdo de 30 pacientes adultos, com diagnostico clÃnico e laboratorial de LMC, em tratamento com inibidores de (TK) de 1 e 2 geraÃÃo. As concentraÃÃes de malonaldeÃdo (MDA) e de nitrito (NO2-) foram realizadas por mÃtodo espectofotomÃtrico. As atividades das enzimas Glutationa peroxidase (GSH-Px) e catalase (CAT) foram determinadas no hemolisado, por kit Glutathione Peroxidase Cellular Activity Assay (Sigma-Aldrich) e por espectofotometria, respectivamente. Glutationa total, glutationa reduzida (GSH reduzida), glutationa oxidada (GSSG) foram determinadas por kit Total Glutathione Activity (Assay Designs, Inc) e calculada a relaÃÃo GSH/GSSG. Para a anÃlise estatÃstica de dados nÃo paramÃtricos foi utilizado o ANOVA e o teste de mÃltiplas comparaÃÃes de Tukey. Foi considerado o nÃvel mÃnimo de significÃncia de 5%. As concentraÃÃes mÃdia de MDA e de NO2- foram aumentadas nos pacientes com LMC em relaÃÃo ao controle, independente da atividade da doenÃa. O perfil antioxidante foi caracterizado pela diminuiÃÃo da CAT e aumento da GSH-Px tambÃm independente da atividade da doenÃa. A GSH reduzida se apresentou diminuÃda, a GSSH, aumentada e a relaÃÃo GSH/GSSG diminuÃda. Os pacientes em uso de inibidores de TK de 2 geraÃÃo apresentaram parÃmetros do estresse oxidativo significativamente elevados em relaÃÃo ao grupo controle. Conclui-se que os pacientes com LMC estÃo sob estresse oxidativo e com atividade antioxidante comprometida.Chronic myeloid leukemia (CML) is characterized by clonal expansion of hematopoietic progenitor cells, result from the translocation (9:22). The oncogene BCR-ABL, in the Ph chromosome, is transcribed and translated into a fusion protein BCR / ABL. The ABL tyrosine kinase (TK) in the fusion protein is constitutively activated and is needed for the initial leukemogenic event of CML and its activity induces production of reactive oxygen species (ROS). Of particular relevance to CML is the fact that an increase of ROS can have consequences, facilitating genomic instability may contribute to disease progression. The aim of this study was to determine the oxidative status in patients with CML, in attendance at a university hospital (HUWC). This is a cross-sectional study consisted of 30 adult patients of both sexes with clinical and laboratory diagnosis of CML on treatment with inhibitors (TK) 1st and 2nd generation. The concentrations of malondialdehyde (MDA) and nitrite (NO2-) were performed by spectrophotometric method. The activities of enzymes glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in hemolysate by Glutathione Peroxidase Cellular Activity Kit  Assay (Sigma-Aldrich) and spectrophotometry, respectively. Total glutathione, reduced glutathione (reduced GSH), glutathione (GSSG) were determined by Total Glutathione Activity Kit  (Assay Designs, Inc) and calculated the ratio GSH / GSSG. For statistical analysis of nonparametric data was used  and ANOVA test for multiple comparisons Tukey. It was considered the minimum level of significance of 5%. The average concentrations of NO2- and MDA were increased in CML patients compared to control, regardless of disease activity. The antioxidant profile was characterized by decreased CAT and GSH-Px increased also independent of disease activity. The reduced GSH is presented decreased, the GSSH, increased and GSH / GSSG decreased. It was observed that patients using protease inhibitors of TK 2nd generation of oxidative stress parameters were significantly elevated compared to controls. In the analysis of patients on imatinib were not detected significant changes in oxidative status. We conclude that patients with CML are under oxidative stress and impaired antioxidant activity