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Delineating aggressiveness of acute myeloid leukemia in a mouse model carrying mutations of Spil (PU.1) and Trp53.
Bašová, Petra
PU.1 downregulation within haematopoietic stem and progenitor cells (HSPCs) is the primary mechanism for the development of acute myeloid leukaemia (AML) in mice with homozygous deletion of the upstream regulatory element (URE) of PU.1 gene. p53 is a well known tumor suppressor that is often mutated in human haematologic malignancies including AML and adds to their aggressiveness; however its genetic deletion does not cause AML in mouse. Deletion of p53 in the PU.1ure/ure mice (PU.1ure/ure p53-/- ) results in more aggressive AML with shortened overall survival. PU.1ure/ure p53-/- progenitors express significantly lower PU.1 levels. In addition to URE deletion we searched for other mechanisms that in absence of p53 contribute to decreased PU.1 levels in PU.1ure/ure p53-/- mice. We found involvement of Myb and miR-155 in downregulation of PU.1 in aggressive murine AML. Upon inhibition of either Myb or miR-155 in vitro the AML progenitors restore PU.1 levels and lose leukaemic cell growth similarly to PU.1 rescue. The MYB/miR-155/PU.1 axis is a target of p53 and is activated early after p53 loss as indicated by transient p53 knockdown. Furthermore, deregulation of both MYB and miR-155 coupled with PU.1 downregulation was observed in human AML, suggesting that MYB/miR-155/PU.1 mechanism may be involved...
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Legal and institutional security of the financial system against money laundering
Kubík, Tomáš ; Kohajda, Michael (advisor) ; Boháč, Radim (referee)
The main objective of this work 'Legal and institutional security of the financial system against money laundering' is to highlight the growing phenomenon of money laundering. It is a phenomenon causing collision of the global economic and financial system, which should not remain unnoticed. This phenomenon must be tackled by all, by legal means. To combat this effect was greatest, then it is necessary that there was a globally recognized legislation that would have embraced most states that there were institutions with qualified personnel with sufficient powers, primarily banking institutions, but not limited to those utmost efforts in the fight against money laundering. If the above conditions are not met, then it will hardly be able to face this phenomenon.
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Delineating aggressiveness of acute myeloid leukemia in a mouse model carrying mutations of Spil (PU.1) and Trp53.
Bašová, Petra ; Stopka, Tomáš (advisor) ; Machová Poláková, Kateřina (referee) ; Zuna, Jan (referee)
PU.1 downregulation within haematopoietic stem and progenitor cells (HSPCs) is the primary mechanism for the development of acute myeloid leukaemia (AML) in mice with homozygous deletion of the upstream regulatory element (URE) of PU.1 gene. p53 is a well known tumor suppressor that is often mutated in human haematologic malignancies including AML and adds to their aggressiveness; however its genetic deletion does not cause AML in mouse. Deletion of p53 in the PU.1ure/ure mice (PU.1ure/ure p53-/- ) results in more aggressive AML with shortened overall survival. PU.1ure/ure p53-/- progenitors express significantly lower PU.1 levels. In addition to URE deletion we searched for other mechanisms that in absence of p53 contribute to decreased PU.1 levels in PU.1ure/ure p53-/- mice. We found involvement of Myb and miR-155 in downregulation of PU.1 in aggressive murine AML. Upon inhibition of either Myb or miR-155 in vitro the AML progenitors restore PU.1 levels and lose leukaemic cell growth similarly to PU.1 rescue. The MYB/miR-155/PU.1 axis is a target of p53 and is activated early after p53 loss as indicated by transient p53 knockdown. Furthermore, deregulation of both MYB and miR-155 coupled with PU.1 downregulation was observed in human AML, suggesting that MYB/miR-155/PU.1 mechanism may be involved...
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The role of TGFß and study of prognostic factors of patients with MDS and AML
Provazníková, Dana ; Fuchs, Ota (advisor) ; Pohlreich, Petr (referee) ; Martásek, Pavel (referee)
We did not find mutation in coding areas of genes for components of TGFbeta1 signaling pathway but we detected decreased or undetectable expression of these analysed genes.The decreased expression is probably caused by epigenetic changes, so by hypermethylation and deacetylation of promoter regionsof these genes.Antiproliferative and apoptotic effect of TGF1 was analysed in AML cell lines (ML1, ML2, CTV1 and Kasumi1). ML2 cells rezistence to inhibition of DNA synthesis by TGFβ1 is not caused by mutations of genes for components of TGFβ1 signaling pathway. We found that increased SnoN (Ski-like novel gene) expression on the level of coresponding mRNA and protein is probably accountable for this rezistence. Kasumi1 and M2 cells were sensitive to induction of apoptózis caused by TGFβ1 treatment but in less extent than by proteazome inhibitor bortezomib. The difference of AML cells of different lines answers shows a great heterogeneity AML in AML patients. Prognostic factors analysis in AML with normal karyotype confirmed that CEBPA (CCAAT/enhancer binding protein alpha) mutations predict favourable prognosis but the elevated EVI1 ("Ecotropic Virus Integration Site 1") and ERG ("ETS-related gene") expression are connected with unfavourable prognosis. EVI1 is a negative marker for MDS as well. We did not confirm...
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Is it possible in clinical practice to perform selection of unrelated donors based on KIR genotypes for AML patients?
FRYČOVÁ, Michaela
Acute myeloid leukemia (AML) is an aggressive malignant disease, during which is for most of the patients only possible treatment the curative allogeneic stem cell transplantation. Besides reaction of the graft against the host is a fundamental limiting factor of the successful transplantation the relapse of the disease. According to several recent published studies, the results of transplantation in patients with AML may be influenced except the HLA genes by others so-called non - HLA genes. Especially there is mounting evidence influence of the donors KIR genes (Killer -cell Immunoglobulin - like receptors) in protection against the relapse after transplantation. HLA and KIR genes are coded on different chromosomes (HLA- sixth chromosome and KIR chromosome 19), therefore are segregated independently and HLA identical donors with recipients usually have different compositions of the KIR genes. Cooley et al. (2010) demonstrated that the specific motifs composition of centromeric and telomeric B haplotypes of KIR genes helps to protect against relapse and increases the chances of complete cure AML. In cases where there are multiple HLA identical unrelated donors (UD) then logically the composition KIR genes by the individual donor could be a criterion in selecting the most appropriate donor, therefore, the one with the greatest potential to protect over the relapse . Based on this study and other data the genetic screening of KIR was started with potential donors, if it was possible to choose from several 10/10 or 10/09 HLA identical UD for the patient. Genotyping was performed by PCR-SSP methodology using commercially available kits. It was performed gene classification 160 preferably identical HLA donors for 55 selected patients with AML. The presence of KIR haplotypes A and B as well as their combinations was determined from the type and number of the KIR genes. All genotypes were entered into the calculator, which allows you to enter up to five potential donors and obtain their assigned into one of three categories according to content KIR B. Groups , "neutral" , "better" , "best" , refer to the appropriate protection against relapse. KIR gene classification in the search for donors revealed 43 donors with AA haplotypes, 90 donors with AB haplotypes and 27 donors with BB haplotypes . After assigning state of the presence KIR B was discovered 107 " neutral " donors , 35 "better " donors and the 18 "best " donors . At 40 (~ 73 %) patients were available donors with the different states of the presence of KIR B. These patients represent a group of patients where the selection criterion of the presence B KIR gene at the donor could be used. We confirmed that the additional selection of HLA-matched unrelated donor on the basis of the content B of KIR genes is feasible. Selection such donor for transplantation may improve the outcome of patients with AML.
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Anti-Money Laundering in the Tax Consultancy Office
Krejčí Reková, Eliška ; Kába, Daniel (referee) ; Polák, Michal (advisor)
Thesis deals with application of anti-money-laundering legislature in tax attorney environment. A general theory of money laundering is discussed and legal requirements on tax attorney are presented resulting from act 253/2008 Coll. on selected measures against legitimization of proceeds of crime and financing of terrorism "Anti-money-laundering Act". Selected tax Attorney Company is then analyzed in terms of anti-money-laundering clauses and their practical application. Finally a specific AML internal control system is created with suggestions on implementation in this company.
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Control system of active magnetic bearing
Kolařík, František ; Vetiška, Jan (referee) ; Houška, Pavel (advisor)
Thesis deals with active magnetic bearing (AMB) levitation control design. Its prototype was done in FSI collaboration with FEKT VUT Brno. The research is focused on communication tools and mathematical model making as well as general AMB issues. Based on this the control design is done an experimentally verified.
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Legitimisation of the proceeds of the crime
Šefčík, Igor ; Žák, Květoslav (advisor) ; Spirit, Michal (referee)
The diploma thesis aims to the problem of money laundering in Czech's law. At the beginning are explained the most frequent terms that are used in this work. The next part is dedicated to the analysis of law environment, institutions and international treaties. The last part contains information about actual methods used in legitimization of the proceeds. The aim of the thesis is to analyze methods of money laundering used in present and assess the quality of instruments used against it in the Czech Republic.
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Business Activity Monitoring
Frühauf, Michal ; Řepa, Václav (advisor) ; Pálka, Jan (referee)
Main focus of the thesis lies in the corporate management decision support deploying and using IT / ICT. Specific technology described is Business Activity Monitoring. The contribution of the work lies primarily in two planes. The first plane is to create as far as the most comprehensive view of the BAM. The findings are collected from different directions and areas. The first direction of research is focused on the development of Business Intelligence and description of BAM as a trend of BI, including the stages of development and projections into the future. The second direction focuses primarily on a detailed circumscribe of BAM. Its definition, deployment assumptions, basic models, the way how business can benefit from BAM usage. The third guideline shows the classification of BAM surrounded by the other / similar technologies and business solutions -- BI and BSM, and the search key differences. The second level of the work is to support the AML implementation in a specific environment of banks using BAM. This is a practical demonstration of the possibility of using BAM in practice. Basic design solution lies in the analysis of risks arising from the law and the current state of the solution. By mapping of banking processes and searching for points of risk it is then possible to deploy these risks BAM tools for their management. Motion of support lies mainly in conceptual terms.
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Project for improving data on clients storage system in relation to anti-money laundering as a branch of risk management in banking
Čejka, Martin ; Švecová, Lenka (advisor) ; Nešetřil, Vlastimil (referee)
Theses in the theoretical part deals with risk management and its concrete form in the banking sector. Closer it is aimed at an area of the implementation of measures against money laundering and terrorist financing (AML). The main task of AML consists in compliance with the legislative framework of the country where the bank operates. In the context of this regulation shall the bank obtain and keep information on a range of clients. The project, which is addressed in practical patr of the theses, is aimed at improving the system of collection and storage of data on clients in co-organization of J&T BANKA. The project is a computerized database application in MS Access, which allows bank staff to work efficiently with information on clients.
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