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Prognosis of childhood acute lymphoblastic leukemia according to novel clinical and biological risk factors
Volejníková, Jana ; Froňková, Eva (advisor) ; Šálek, Cyril (referee) ; Klener, Pavel (referee)
Great progress has been achieved in the diagnostics and therapy of childhood acute lymphoblastic leukemia (ALL) during the last few decades and the permanent cure rate for children and adolescents has risen to nearly 90%. The basic principle of ALL treatment is to split patients into several groups receiving treatment of different intensity according to exactly defined prognostic features. This is aimed at reducing both the risk of relapse and toxic complications of treatment. The development of new diagnostic methods, especially in the field of molecular genetics and flow cytometry, allowed further improvements in the risk stratification - the minimal residual disease (MRD) has become a crucial prognostic factor in modern treatment protocols for pediatric ALL as a sensitive marker of both response to therapy and subclinical leukemic involvement of various tissues of the organism. Nevertheless, there is still an intensive search for new markers that would enable even more precise characterization of the leukemic clone, and treatment strategies reflecting the biology of leukemic cells are being optimized. The first part of our study describes the monitoring and prognostic impact of MRD in peripheral blood of children with ALL with emphasis on very early time points of treatment. MRD was examined by the...
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The role of WT1 and its isoforms in normal haematopoiesis and leukaemogenesis
Kramarzová, Karolina ; Trka, Jan (advisor) ; Pospíšilová, Dagmar (referee) ; Živný, Jan (referee)
61 Summary Wilms' tumor gene 1 (WT1) is highly expressed in acute leukemia and other hematological malignancies. It has been therefore suggested as a potential universal marker of minimal residual disease (MRD), particularly in patients with acute myeloid leukemia (AML). Due to controversial results of some of the studies, the role of WT1 in MRD follow-up and WT1 prognostic significance remain unclear. WT1 protein is produced in more than 36 different isoforms. These variants have distinct, partially overlapping functions and their ratio is supposed to influence the final effect of WT1. However, despite the increasing number of studies, the clinical impact of WT1 and its isoforms in acute leukemia have not yet been elucidated. We established a unique qPCR method to assess the expression pattern of the main 4 WT1 isoforms. Using this method, we determined the ratio of WT1 variants in the samples of patients with AML, myelodysplastic syndrome (MDS) and healthy controls. Our data showed that this pattern can distinguish among particular hematological malignancies, but lacks a prognostic significance. Within our international study group we determined the prognostic significance of total WT1 expression in childhood AML. Based on our results of a large cohort of patients we can conclude that WT1 expression at...
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