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Aberrations of chromosome 5 in adult patients with myelodysplastic syndromes (MDS)
Šejgunovová, Nikola ; Zemanová, Zuzana (advisor) ; Urbánková, Helena (referee)
Myelodysplastic syndrome (MDS) is a clonal disease of hematopoesis resulting from damage to hematopoietic stem cells. The most common chromosomal aberration in patients with MDS is deletion of the long arms of chromosome 5, del(5q). The aim of this study is to analyse unbalanced aberrations of chromosome 5 in MDS patients, to compare the extent of 5q deletion in groups of patients with isolated del(5q) and with del(5q) in complex karyotypes, and to study the effect of the extent of del(5q) on overall survival and prognosis of the disease. We combined cytogenomic methods to examine 88 bone marrow samples from patients with MDS and del(5q) confirmed by conventional banding methods. Del(5q) was present in the karyotype as an isolated aberration in 31 patients (35,2 %), in combination with one other clonal aberration in 9 patients (10,2 %), and as part of complex karyotypes in 48 patients (54,6 %). Patients with complex karyotypes had a lower overall survival than patients with isolated del(5q). The occurrence of complex karyotypes was associated with a large extent of 5q deletion. When both the occurrence of complex karyotypes and the extent of 5q deletion were considered, only karyotype complexity had a significant effect on patients' overall survival. The extent of the deletion does not affect...
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Clonal evolution of leukemic cells and its role in the progression of leukemia and preleukemia
Svobodová, Karla ; Zemanová, Zuzana (advisor) ; Urbánková, Helena (referee) ; Šubrt, Ivan (referee)
Clonal evolution is a multistep process characterized by progression of the disease, adverse prognosis and shortening of overall survival. The aim of the dissertation was a detailed characterization of identified changes in patients with myelodysplastic syndromes (MDS) and clonal evolution and evaluation of their prognostic impact. We performed detail cytogenomic analyses in 36/469 (8%) patients with confirmed linear clonal evolution. We described 57 primary abnormalities (32% MDS-specific) at the time of diagnosis, the most frequent was deletion of long arm of chromosome 5. We proved 156 secondary aberrations (21% MDS-specific) during the course of the clonal evolution, the most frequent were trisomies/tetrasomies of chromosome 8. We identified acquired uniparental disomies (aUPD) in 19% of patients. In MDS-specific aUPDs 4q, 11q and 17p, we proved homozygous mutations of TET2, c-CBL and TP53 genes. We found a statistically significant difference in overall survival between the groups of patients divided according to their diagnostic cytogenomic findings. In patients with clonal evolution before treatment 54% of aberrations were gains of whole chromosomes, by contrast 44% of abnormalities identified in patients with clonal evolution after treatment were monosomies or deletions. The study of clonal...
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