Avaliação dos genes MLL, RB e TP53 em pacientes com síndrome mielodisplásica

• Main Author: Lima, Diego Silva
• Publication Date: 2011
• Format: Master thesis
• Language: por
• Source: Repositório Institucional da Universidade Federal do Ceará (UFC)
• dARK ID: ark:/83112/001300000pvrr
• Download full: http://www.repositorio.ufc.br/handle/riufc/6887
• topic: Síndromes Mielodisplásicas; Citogenética; Genes do Retinoblastoma; Genes p53

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders affecting the hematopoietic pluripotent cell, characterized by low cell counts in peripheral blood, dysplasia in one or more cell lines, inefficient hematopoiesis and increased risk of progression to acute myeloid leukemia. Although the disease can affect patients of other age groups, they are more frequent in those with advanced age with an average 60 to 75 years at diagnosis. Chromosomal abnormalities are observed in approximately 50% of all cases of MDS and are related with clinical and morphological findings. The aim of this study was to determine, through the technique of FISH (fluorescence in situ hybridization), the frequency of changes involving the MLL, RB, and TP53 genes in patients with MDS and associate these changes with cytogenetic findings. The cases included in the study were selected in the ambulatory of SMD from University Hospital Walter Cantídio. Thirty three patients were selected, 17 had aged over 60 years. 52% of patients were classified, according to WHO criteria, as refractory cytopenia with dysplasia in multiple lineages (RCDM) and 61% stratified, according to IPSS, as intermediate risk 1 (INT-1). 78% of patients had abnormalities detected by cytogenetics, among them 31% had complex karyotypes (more than 3 changes per metaphase). 18% of patients had changes at least in one of the three genes valued in this study by FISH. Three patients showed alterations of TP53 gene, being detected in two patients (records 31 and 6) the deletion of a single allele or both alleles of the gene, respectively, and in the third (record 2), we detected amplification of TP53 gene, all this changes were not detected by classical cytogenetics, because it is a less sensitive technique. 6% of patients (records 7 and 22) had rearrangement of MLL gene. In the first case, FISH discarded the gene deletion alleged by cytogenetic, proving that it was present in the genome of the patient, but in a rearranged form, and in the second case cytogenetics failed to demonstrate rearrangement of the gene. For the RB gene, FISH identified only one patient (3%) with deletion of one allele of the gene, and this change was also not detected by classical cytogenetics. During evaluating the TP53 gene, FISH allowed identification of two patients (records 5 and 10) presenting at least six extra copies of chromosome 17, probably representing a small hyperdiploid clone partially detected in the first patient and not detected in the second . In the six patients who showed abnormalities of the genes analyzed, FISH has provided information that added, changed or confirmed the result previously given by classical cytogenetics, which are a major application of this technique due to its high sensitivity compared to the traditional method.