Expression of WT1 and its splicing variants in myeloid leukemias

3 Abstract Myeloid leukemias include malignant diseases characterized by clonal expansion of the myeloid cell lineage. While in case of chronic myeloid leukemia (CML), the main cause of the disease has already been identified - t(9;22) and the aktivity of the fusion product of the translocation BCR-ABL, acute myeloid leukemia (AML) has been associated with plenty of different translocations and mutations. The aim of this work was to contribute to the improvement of monitoring of patients with myeloid leukemias via detailed study of the panleukemic marker Wilms tumor gene 1 (wt1) expression. Prognostic value of wt1 expression has been proved for AML patients, however, it has not yet been confirmed for CML patients. Expression of different wt1 variants (more then 36 protein products) is known very poorly in both, AML and CML as well as in normal hematopoiesis. Most of the study is focused on CML, only limited parts are dedicated to AML. In the first part of the work, we clearly proved prognostic value of total wt1 mRNA expression for CML patients. Statistical evaluations revealed critical wt1 values which enable to specify prognosis of patients responding non-optimally to imatinib. Bcr-abl looses much of its prognostic value in these patients. Further, we have designed and optimized PCRs for selected wt1..