|
|
Early Detection of Disease Progression in Patients with Myelodysplastic Syndromes.
Kaisrlíková, Monika ; Beličková, Monika (advisor) ; Kalinová, Markéta (referee) ; Zemanová, Zuzana (referee)
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders with a risk of transformation into acute myeloid leukemia (AML). The International Prognostic Scoring Systems integrate clinical data and cytogenetics to determine the risk of AML transformation for individual patients. Precise risk assessment is crucial for treatment decision- making. The aim of this thesis was to identify molecular markers for the early detection of disease progression in MDS patients. Using cDNA microarrays and next-generation sequencing, we targeted long noncoding RNAs (lncRNAs) and recurrently mutated genes in bone marrow cells. In addition, we focused on the identification of pathways related to the progression of MDS and understanding how the identified biomarkers participate. In the transcriptome study, we identify 4 candidate lncRNAs that may serve as prognostic biomarkers of the adverse course of MDS: H19, WT1-AS, TCL6, and LEF1-AS. Using various statistical approaches, we determined the level of H19 to be a strong independent prognostic marker. Furthermore, our data showed that disruption of transcriptional coregulation of the imprinting locus H19/IGF2 and miR-675, which directly regulates H19 and plays a role in tumorigenesis, accompanies disease progression. In the genomic study...
|
guest ::
