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The role of the nurse educator in a patient with chronic myeloid leukemia
Kadlec, Daniel ; Zámečníková, Kateřina (advisor) ; Tomová, Šárka (referee)
The bachelor thesis in the overview of the literature deals with the topics associated with chronic myeloid leukemia as well as with the education and the role of a nurse. This part also consists of other topics that help the reader understand comprehensively the whole topic relating to the empirical part. Method: The mainstay of the empirical part is the questionnnaire of own structure serving for the achievement of partial aims of this thesis. 89 respondents (100%) from FN Plzeň, VFN Praha and FN Královské Vinohrady participated in this survey. I set the aims that should ascertain educational prerequisites of nurses, the most used educational method and the satisfaction with the educational materials. Then on the basis of findings from the survey I was also trying to find out what would motivate nurses to improve their educational abilities. In conclusion I drew up the educational standard proposition for a faculty workplace complemented by the proposition of an educational training for nurses. The main goal is to improve the education of nurses. In the empirical part I pursue the analysis of the respondents' answers as well as the hypotheses verifying a link of the nurses' satisfaction with didactic materials and also how the nurses' education influences their motivation for additional...
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Molecular events associated with resistance to tyrosine kinase inhibitors in leukemia cells.
Hrdinová, Tereza
Chronic myeloid leukemia (CML) is a myeloproliferative stem cell disease characterized by the expression of BCR-ABL oncoprotein with constitutive tyrosine kinase activity. Although the development of tyrosine kinase inhibitors (TKI) such as imatinib dramatically improved the treatment of CML, a certain subset of patients develops resistance to TKI drugs. The most common cause of TKI resistance are point mutations in the BCR-ABL1 gene, followed by other mutation-independent mechanisms. Survival and proliferation of CML cells in the presence of TKI drugs are accompanied by adaptive changes in their metabolism. Drug resistance can be maintained by extrinsic signals, among which exosomes, small vesicles released by (drug-resistant) cells, have been shown to play an important role. The aim of this thesis was to characterize two CML cell lines sensitive and resistant to imatinib, as well as the exosomes derived from imatinib-resistant CML cells by proteomic approaches. Identification of metabolic vulnerabilities in drug-resistant cells enables their targeting by clinically available drugs, thus offering potential therapeutic targets for their selective elimination. Analysis of exosomes derived from imatinib-resistant cells can identify specific membrane surface proteins exploitable as clinically relevant...
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Molecular events associated with resistance to tyrosine kinase inhibitors in leukemia cells.
Hrdinová, Tereza ; Vyoral, Daniel (advisor) ; Klener, Pavel (referee) ; Holoubek, Aleš (referee)
Chronic myeloid leukemia (CML) is a myeloproliferative stem cell disease characterized by the expression of BCR-ABL oncoprotein with constitutive tyrosine kinase activity. Although the development of tyrosine kinase inhibitors (TKI) such as imatinib dramatically improved the treatment of CML, a certain subset of patients develops resistance to TKI drugs. The most common cause of TKI resistance are point mutations in the BCR-ABL1 gene, followed by other mutation-independent mechanisms. Survival and proliferation of CML cells in the presence of TKI drugs are accompanied by adaptive changes in their metabolism. Drug resistance can be maintained by extrinsic signals, among which exosomes, small vesicles released by (drug-resistant) cells, have been shown to play an important role. The aim of this thesis was to characterize two CML cell lines sensitive and resistant to imatinib, as well as the exosomes derived from imatinib-resistant CML cells by proteomic approaches. Identification of metabolic vulnerabilities in drug-resistant cells enables their targeting by clinically available drugs, thus offering potential therapeutic targets for their selective elimination. Analysis of exosomes derived from imatinib-resistant cells can identify specific membrane surface proteins exploitable as clinically relevant...
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Myeloid lineage involvement in BCR/ABL-positive acute lymphoblastic leukaemia
Hovorková, Lenka ; Zuna, Jan (advisor) ; Mikyšková, Romana (referee)
The Philadelphia chromosome has been discovered in 1960. This chromosomal aberration was mistakenly associated only with chronic myeloid leukaemia (CML) for decade. However, this type of translocation including chromosomes 9 and 22 was found in patients with different type of neoplasia - acute lymphoblastic leukaemia (ALL). Different lineage involvement has been found in these two types of leukaemia. Whereas in Ph-positive ALL, the Philadelphia chromosome is restricted to the lymphoid lineage, in CML patients mostly myeloid cells are those being Ph-positive. Hence it seems quite trivial to distinguish between ALL and CML. But there is a phase of CML called lymphoid blast crisis which is indistinguishable from ALL. The possibility of distinguishing between CML in lymphoid blast crisis and ALL would inhere in determining myeloid lineage involvement. Actually it had been shown that some patients with Ph+ ALL have involved also a myeloid lineage. Different types of treating protocols are used in CML and ALL. In addition, prognoses for both types of leukaemia are different. Thus it is crucial to distinguish between this two disorders and revealing of any difference can impact the treatment outcome of above mentioned malignancies. Detection of minimal residual disease according to involvement of myeloid or CD34+...
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Analysis of the effects of Src kinase inhibitors on adhesion signaling in human hematopoietic cells
Obr, Adam ; Kuželová, Kateřina (advisor) ; Jiroušková, Markéta (referee)
Adhesion of hematopoietic cells to the bone marrow microenvironment is important for their proper development. It is proven that Src-family kinases (SFK) regulate cell adhesion, although their exact role in the regulation of adhesion signaling remains unclear. Since adhesion processes are investigated mainly in adherent cell types, far less is known about hematopoietic cells. However, defects in the cell adhesion accompany a number of hematological diseases, like chronic myeloid leukaemia (CML). SFK overexpression is one of the proposed mechanisms of resistance to the first-line CML treatment, imatinib mesylate. Second generation drugs (e. g. dasatinib) inhibit SFK together with Bcr-Abl. Additionally, SFK-specific inhibitors (PP2, Src inhibitor-1) are also available, but there are no studies about effects of these drugs on cellular adhesivity of hematopoietic precursors. To explore the dynamics of hematopoietic cell adhesion to the extracellular matrix, we introduced a new approach using the RTCA xCELLigence DP system along with the well-established method of fluorimetric detection of adherent cell fraction. Our general observation is that various drugs (dasatinib, imatinib, PP2, Src inhibitor-1) induce pro-adhesive effects in several leukemic cell lines. Direct comparison of the kinetics of...
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Leukaemias with BCR/ABL fusion gene.
Hovorková, Lenka ; Zuna, Jan (advisor) ; Zemanová, Karla (referee)
Philadelphia (Ph) chromosome, as a result of reciprocal translocation, is in majority of cases connected to two types of leukaemia - chronic myelogenous (CML) and acute lymphoblastic (ALL). The translocation occurs within large intronic sequences of BCR and ABL genes. The breakpoints are specific for individual patient and may be used as a target for monitoring of leukemic burden (MRD, minimal residual disease) during the treatment. In general, MRD is an important prognostic factor, which influences the treatment intensity. Two standardized methods are currently used for its monitoring. The first one is based on the detection of clonal specific Immunoglobulin and/or T-cell receptor genes rearrangements (and thus cannot be used for CML cases) at the DNA level, the second one utilizes detection of the BCR/ABL fusion gene at the mRNA level. Our aim was to optimize and standardize the process to find individual patient breakpoints on Ph chromosome and to use it for MRD quantification. We found the breakpoint in 80 % cases. The MRD data from 15 patients obtained by our method were compared to the levels obtained by standard methods (Ig/TCR and BCR/ABL transcript quantification). In all but 1 patient we found significant discrepancies, raising the questions about leukemic origin and the most accurate method for...
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Quantitation of transcript bcr / abl in chronic myeloid leukemia
PYTLOVÁ, Kamila
This bachelor thesis in the theoretical part deals with the disease chronic myelogenous leukemia (CML), which accounts for about 25% of the leukemia of the adult age, with maximum incidence in the age group between 50.-70. year of life. With low frequency occurs even in children and adolescents. Chronic myeloid leukemia is characterized by the presence of the hybrid gene bcr/abl, that arises as a result of reciprocal translocation t(9;22)(q34;q11) karyotypicaly detectable as a Ph chromosome. The gene bcr/abl is the hallmark of CML used to refine the diagnosis and monitoring of treatment success. Quantification is carried out either as a relative (often), when the amount of fluorescence of the test gene is compared with the amount of fluorescence of the reference gene, or absolute, when the amount of DNA we are going deduct from the calibration curve, which will provide us with a DNA sample of a given concentration. The aim of this work is to compare different ways of quantification of the transcript bcr/abl. The pursuit of quantification of this transcript has been going on for a long time, involved here organization from around the world. The most sensitive method for detection of the presence of this aberration is the reverse transcription polymerase chain reaction (RT-PCR) detecting the transcript bcr/abl. The second objective of this work is to give an overview of this issue and perform one of the methods for the relative quantification of the gene bcr/abl. The final objective is to get acquainted with the management of samples in the laboratory, and verification and validation of these methods.
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