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Significance of somatic mutations in chronic lymphocytic leukemia
Tauchmanová, Petra ; Savvulidi Vargová, Karina (advisor) ; Javorková, Eliška (referee)
Chronic lymphocytic leukemia (CLL) represents the most prevalent leukemia in Europe and USA. CLL affects predominatly elderly people (median age, 70y). This lymphoproliferative disorder is characterised by an accumulation of mature B-cells in the peripheral blood, bone marrow and lymph nodes. The lifespan of CLL cells is longer than normal healthy B-cells due to impaired cell cycle and apoptosis. CLL cells dysplay several chromosomal aberations and genetic abnormalities. The next generation sequencing revealed many somatic mutations in CLL cells. Analysis of these somatic mutations in CLL facilitates detail understanding at the disease molecular basis and opens new possibilities to the personalised therapy. The main aim of this thesis is brief description of CLL as disease and to summarise the recent knowledge in the field of next generation sequencing with attention to CLL.
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Analysis of structural chromosomal rearrangements in hematological neoplasias; Study of structural chromosomal rearrangements of cells of chronic lymphocytic leukemia after DSP30/IL2 stimulated cultivation
Hrubá, Martina ; Michalová, Kyra (advisor) ; Goetz, Petr (referee) ; Březinová, Jana (referee)
Cytogenetic analysis of cells of chronic lymphocytic leukemia (CLL) is difficult because of their low proliferative activity. To obtain sufficient number of mitoses for performing chromosomal analysis a suitable stimulation of cell division is needed. Using DSP30/IL2 stimulated cultivation 391 CLL samples were investigated in 5 years' period. The cultivation was showed to have high success rate (96%; 375/391) with also high rate of detection of pathological clones by both karyotype and metaphase FISH analyses (in 84% of samples; 329/391). Almost in half of samples (44%; 171/391) other aberrations than recurrent FISH (i.e. 13q14 deletion, trisomy 12, TP53, ATM genes deletions) were found. Also high frequency of translocations (37%; 144/391), complex karyotypes (28%; 111/391) and clonal evolution, which was detected in one third of all samples (34% of samples with presence of more than two clones; 133/391) and like a new event in disease duration even more frequently (in 39% of samples repeatedly investigated after stimulated cultivation; 21/54), was revealed. The presence of translocations, complex karyotypes and clonal evolution was associated with progressive form of disease (P 0,000003, resp. P 0,0002 and P 0,05/P 0,04). In cases of the recurrent deletions the detailed analysis of metaphase...
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Analysis of structural chromosomal rearrangements in hematological neoplasias; Study of structural chromosomal rearrangements of cells of chronic lymphocytic leukemia after DSP30/IL2 stimulated cultivation
Hrubá, Martina
Cytogenetic analysis of cells of chronic lymphocytic leukemia (CLL) is difficult because of their low proliferative activity. To obtain sufficient number of mitoses for performing chromosomal analysis a suitable stimulation of cell division is needed. Using DSP30/IL2 stimulated cultivation 391 CLL samples were investigated in 5 years' period. The cultivation was showed to have high success rate (96%; 375/391) with also high rate of detection of pathological clones by both karyotype and metaphase FISH analyses (in 84% of samples; 329/391). Almost in half of samples (44%; 171/391) other aberrations than recurrent FISH (i.e. 13q14 deletion, trisomy 12, TP53, ATM genes deletions) were found. Also high frequency of translocations (37%; 144/391), complex karyotypes (28%; 111/391) and clonal evolution, which was detected in one third of all samples (34% of samples with presence of more than two clones; 133/391) and like a new event in disease duration even more frequently (in 39% of samples repeatedly investigated after stimulated cultivation; 21/54), was revealed. The presence of translocations, complex karyotypes and clonal evolution was associated with progressive form of disease (P 0,000003, resp. P 0,0002 and P 0,05/P 0,04). In cases of the recurrent deletions the detailed analysis of metaphase...
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Significance of somatic mutations in chronic lymphocytic leukemia
Tauchmanová, Petra ; Savvulidi Vargová, Karina (advisor) ; Javorková, Eliška (referee)
Chronic lymphocytic leukemia (CLL) represents the most prevalent leukemia in Europe and USA. CLL affects predominatly elderly people (median age, 70y). This lymphoproliferative disorder is characterised by an accumulation of mature B-cells in the peripheral blood, bone marrow and lymph nodes. The lifespan of CLL cells is longer than normal healthy B-cells due to impaired cell cycle and apoptosis. CLL cells dysplay several chromosomal aberations and genetic abnormalities. The next generation sequencing revealed many somatic mutations in CLL cells. Analysis of these somatic mutations in CLL facilitates detail understanding at the disease molecular basis and opens new possibilities to the personalised therapy. The main aim of this thesis is brief description of CLL as disease and to summarise the recent knowledge in the field of next generation sequencing with attention to CLL.
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Analysis of structural chromosomal rearrangements in hematological neoplasias; Study of structural chromosomal rearrangements of cells of chronic lymphocytic leukemia after DSP30/IL2 stimulated cultivation
Hrubá, Martina
Cytogenetic analysis of cells of chronic lymphocytic leukemia (CLL) is difficult because of their low proliferative activity. To obtain sufficient number of mitoses for performing chromosomal analysis a suitable stimulation of cell division is needed. Using DSP30/IL2 stimulated cultivation 391 CLL samples were investigated in 5 years' period. The cultivation was showed to have high success rate (96%; 375/391) with also high rate of detection of pathological clones by both karyotype and metaphase FISH analyses (in 84% of samples; 329/391). Almost in half of samples (44%; 171/391) other aberrations than recurrent FISH (i.e. 13q14 deletion, trisomy 12, TP53, ATM genes deletions) were found. Also high frequency of translocations (37%; 144/391), complex karyotypes (28%; 111/391) and clonal evolution, which was detected in one third of all samples (34% of samples with presence of more than two clones; 133/391) and like a new event in disease duration even more frequently (in 39% of samples repeatedly investigated after stimulated cultivation; 21/54), was revealed. The presence of translocations, complex karyotypes and clonal evolution was associated with progressive form of disease (P 0,000003, resp. P 0,0002 and P 0,05/P 0,04). In cases of the recurrent deletions the detailed analysis of metaphase...
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