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Identification and Characterization of Genetic Aberrations in Acute Childhood Leukemia
Lukeš, Julius ; Kubričanová Žaliová, Markéta (advisor) ; Machová Poláková, Kateřina (referee) ; Živný, Jan (referee)
Childhood acute leukemias are genetically complex disorders, with recurrent or random aberrations found in most patients. Their proper functional characterization is crucial for understanding the role they play in the process of leukemogenesis. We aimed to identify and characterize the genetic background of two leukemic entities. The transient myeloproliferative disorder (TMD) is a preleukemic condition that occurs in 10% of newborns with Down syndrome. Trisomy 21 together with in-utero gained mutations in the GATA1 gene are essential in TMD and represent an ideal "multi-hit" model to study leukemogenesis. We investigated an alternative pathogenic mechanism enabling TMD development in a confirmed absence of trisomy 21. Novel deletions in the GATA1 and JAK1 genes were described as potential drivers of this TMD. The deletion D65_C228 in GATA1 results in the expression of an aberrant isoform, which is predicted to lose transactivation potential and, more importantly, to partially lose the ability of recognizing physiological DNA binding sites, possibly triggering TMD alone. Our thorough characterization of JAK1 F636del questions its role in TMD development. Analysis of JAK/STAT signaling suggested decrease of kinase activity upon F636 loss. Cells harboring the aberrant JAK1 did not obtain cytokine-...
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Interventional program of aerobics for people with Down syndrome
Valtová, Nela ; Doležalová, Kateřina (advisor) ; Černá, Jana (referee)
Title: Aerobics intervention motoric program for individuals with Down syndrome. Objectives: The aim of the bachelor's thesis is to create and verify an aerobics intervention program based on an analysis of theoretical background and an interview with specialists in the sphere of sports and education of people with DS. Methods: The work is focused on the creation and implementation of an aerobics intervention program for people with Down syndrome (DS) based on an analysis of theoretical background and an interview with specialists. The planned methods of data collection that were used are a semi-structured interview, analysis of theoretical background, induction, description of knowledge and own creative work during creating the program. Results: The research shows that people with Down syndrome enjoy sports. Despite the advances brought by modern times, the offer of physical activities for people with Down syndrome seems to be poor. Due to the health complications that Down syndrome brings with it, aerobic activities for individuals with the mentioned diagnosis seem to be suitable and developmental for their physical and mental side. Individuals with Down syndrome have a warm relationship with music, which becomes their motivation in almost every activity. The specialists found the program...
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Identification and Characterization of Genetic Aberrations in Acute Childhood Leukemia
Lukeš, Julius ; Kubričanová Žaliová, Markéta (advisor) ; Machová Poláková, Kateřina (referee) ; Živný, Jan (referee)
Childhood acute leukemias are genetically complex disorders, with recurrent or random aberrations found in most patients. Their proper functional characterization is crucial for understanding the role they play in the process of leukemogenesis. We aimed to identify and characterize the genetic background of two leukemic entities. The transient myeloproliferative disorder (TMD) is a preleukemic condition that occurs in 10% of newborns with Down syndrome. Trisomy 21 together with in-utero gained mutations in the GATA1 gene are essential in TMD and represent an ideal "multi-hit" model to study leukemogenesis. We investigated an alternative pathogenic mechanism enabling TMD development in a confirmed absence of trisomy 21. Novel deletions in the GATA1 and JAK1 genes were described as potential drivers of this TMD. The deletion D65_C228 in GATA1 results in the expression of an aberrant isoform, which is predicted to lose transactivation potential and, more importantly, to partially lose the ability of recognizing physiological DNA binding sites, possibly triggering TMD alone. Our thorough characterization of JAK1 F636del questions its role in TMD development. Analysis of JAK/STAT signaling suggested decrease of kinase activity upon F636 loss. Cells harboring the aberrant JAK1 did not obtain cytokine-...
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