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The Role of WT1 gene in normal hematopoiesis and leukemogenesis
Kramarzová, Karolina ; Trka, Jan (advisor) ; Zadražil, Stanislav (referee)
6 Abstract The Wilms' tumor gene is highly expressed in a large proportion of human acute leukemias and other hematological malignancies. It is thought to play an important role in human hematpoiesis and leukemogenesis. Despite the large number of studies, WT1 expression patterns and its clinical significance in acute myeloid leukemia remain still controversial. To investigate the prognostic relevance of initial WT1 expression and its usefulness as a marker for minimal residual disease, we have analysed 66 bone marrow samples from newly diagnosed AML patients. RQ-RT-PCR for absolute quantification of total WT1 was designed according to Europe Against Cancer Program. In 82 % of samples we detected a higher expression of WT1 compared to normal healthy donors or patients with acute lymphoblastic leukemia (p<0.0001). We did not find any correlation between initial WT1 expression level and age or sex. Patients with FAB M3 subtype showed significantly higher WT1 levels than other subtypes, especially M5 (p<0.001). We found a strikingly high WT1 expression in standard risk group patients compared to high risk group (p<0.0007). Children with FAB/cytogenetical favorable prognostic factors have high WT1 expression, while there was no relation between WT1 levels at diagnosis and day 15 BM response. We did not find any...
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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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The Role of WT1 gene in normal hematopoiesis and leukemogenesis
Kramarzová, Karolina ; Trka, Jan (advisor) ; Zadražil, Stanislav (referee)
6 Abstract The Wilms' tumor gene is highly expressed in a large proportion of human acute leukemias and other hematological malignancies. It is thought to play an important role in human hematpoiesis and leukemogenesis. Despite the large number of studies, WT1 expression patterns and its clinical significance in acute myeloid leukemia remain still controversial. To investigate the prognostic relevance of initial WT1 expression and its usefulness as a marker for minimal residual disease, we have analysed 66 bone marrow samples from newly diagnosed AML patients. RQ-RT-PCR for absolute quantification of total WT1 was designed according to Europe Against Cancer Program. In 82 % of samples we detected a higher expression of WT1 compared to normal healthy donors or patients with acute lymphoblastic leukemia (p<0.0001). We did not find any correlation between initial WT1 expression level and age or sex. Patients with FAB M3 subtype showed significantly higher WT1 levels than other subtypes, especially M5 (p<0.001). We found a strikingly high WT1 expression in standard risk group patients compared to high risk group (p<0.0007). Children with FAB/cytogenetical favorable prognostic factors have high WT1 expression, while there was no relation between WT1 levels at diagnosis and day 15 BM response. We did not find any...
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