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The use of novel technologies in the identification of unique molecular markers for minimal residual disease assessment in acute leukemia patients
Jančušková, Tereza ; Peková, Soňa (advisor) ; Jarošová, Marie (referee) ; Lysák, Daniel (referee)
Acute leukemias (AL) comprise a heterogeneous group of hematologic malignancies, and individual patient responses to treatment can be difficult to predict. Monitoring of minimal residual disease (MRD) is thus very important and holds great potential for improving treatment strategies. Common MRD targets include immunoglobulin heavy chain or T-cell receptor gene rearrangements, recurrent cytogenetic abnormalities and mutations in important hematological genes. Whereas in the majority of adult acute lymphoblastic leukemia patients a suitable MRD target can be identified, in adult acute myeloid leukemia patients well-characterized targets are found in only half of cases. The identification of new specific molecular markers of leukemic blasts for MRD assessment, particularly in AML patients, is therefore highly desirable. Our aim was to develop a flexible strategy for mapping of cytogenetically identified unique clone-specific abnormalities down to the single nucleotide level and, based on the sequence, design a specific real-time PCR assay for MRD assessment in AL patients without any previously described MRD marker. Using a combination of cytogenetic (chromosome banding, chromosome microdissection), molecular cytogenetic (mFISH, mBAND) and molecular biological (next- generation sequencing, long-range...
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Molecular-cytogenetic analysis of chromosome 11 aberrations in hematological malignancies
Šárová, Iveta ; Březinová, Jana (advisor) ; Goetz, Petr (referee) ; Jarošová, Marie (referee)
Chromosome 11 abnormalities are found in many hematological malignancies. In acute myeloid leukemia (AML), a proto-oncogene MLL (11q23.3) is frequently altered. However, rearrangements to other regions of chromosome 11 have been reported. Therefore, we have identified and characterized the chromosome 11 breakpoints and common deleted and amplified areas in the bone marrow or peripheral blood cells of newly diagnosed patients with AML. Many recurrent and random chromosome 11 breakpoints were identified (recurrent in bands 11p15.4 (in NUP98 gene), 11q23.3 (in the MLL gene), 11p13, 11p12 and 11q13.2) and deleted or duplicated/amplified regions were determined. We notified new possibly significant genes in the development of AML. Contrary to the MLL rearrangements, patients with other chromosome 11 changes were older, with complex karyotype, unbalanced aberrations and short survival. FISH screening was proved very helpful in case of deviding cells lack and cryptic MLL gene rearrangement. In conclusion, molecular analyses of chromosomal breakpoints and amplified or deleted areas are very important not only for the patient stratification into specific prognostic and clinical subgroups but also for the identification of genes involved in tumour pathogenesis. Further investigation of the affected genes and...
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Gene expression analysis in patients with myelodysplastic syndrome
Vašíková, Alžběta ; Votavová, Hana (advisor) ; Neuwirtová, Radana (referee) ; Jarošová, Marie (referee)
Myelodysplastic syndrome (MDS) is a clonal disorder affecting maturation and differentiation of hematopoietic stem cells. MDS is characterized by ineffective hematopoiesis resulting in peripheral blood cytopenia in at least one lineage, and increased risk of development of acute myeloid leukemia (AML). This disorder mostly affects the elderly, with the incidence of 10-50/100000 people per year. Heterogeneity of MDS is further underlined by the presence of both idiopathic primary and secondary therapy-related forms, which arise from accumulation of mutational events induced by cytotoxic therapy (exposure to alkylating agents or after therapy with topoisomerase II inhibitors). In this thesis, we focused on determination of differential gene expression between MDS patients and control subjects using different microarray platforms. Using nylon membranes, we detected 4 genes (ERCC1, FLT1, NME4, PCNA) with increasing expression pattern in advanced MDS stages, which correlated with disease progression. Their strong up- regulation was also observed in patients with de novo AML, suggesting their involvement in the leukemic transformation of MDS. Comparison of gene expression profiles of early and advanced MDS obtained by Agilent microarrays resulted in the set of differentially expressed genes, which might...
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Play and Layers of Playing in Animation
Jarošová, Marie ; KUBÍČEK, Jiří (advisor) ; PAVLÁTOVÁ, Michaela (referee)
The thesis "Play and Layers of Playing in Animation" attempts to identify where in the world of animation we meet the phenomenon of a play and which kinds of forms it could have. We answer to this question through the analysis of the first film of the series "Pojďme pane, budeme si hrát" by Břetislav Pojar, "Potkali se u Kolína" and we discuss its general validity.
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Acting in Animation
Jarošová, Marie ; HANČIL, Jan (advisor) ; MUSILOVÁ, Martina (referee)
The master's thesis Acting in Animation reflects the author's experience, gained by combining studies of animation and of authorial acting. Her goal is to explore and propose what should be included in the theory of acting in animation. She then seeks general guidelines which animators and authors of animated films can apply in their work.
Can we call an animator "actor"? What general principles can we observe in the dramatic expression of animated characters? Who is an authorial animator?
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Kvantitativní uvolňování a riziko růstu inflace v USA
Jarošová, Marie
The thesis is focused on quantitative easing, which used the U.S. central bank for the third time in a few years, to deepen the expansionary monetary policy. There is examining the relationship between quantitative easing and inflation, as the sharp rise in inflation is considered a major risk associated with quantitative release an. Relationship between quantitative easing and inflation is observed by means of simple regress analysis (using the OLS) and the moving correlation (rolling correlation) between each wheel QE with regard to the development of mortgage, financial and debt crisis.
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