EVI1 in Acute Myeloid Leukemia

To diagnose patients with acute myeloid leukemia (AML) in an optimal manner, the combined application of conventional and modern cytogenetics with state-of-the-art molecular diagnostics is a requirement. Although at present, the WHO accurately classifies an array of human AML patients based on karyotyping combined with molecular diagnostic procedures, insight into the molecular defects of human AML is still increasing. As a result of that, the classifi cation of AML will be approved in the upcoming years. The focus of this thesis was to increase our understanding of specific subtypes of human leukemia. We focused on AMLs with chromosome 3q rearrangements, in particular on patients with an inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 (shortly: (inv(3)/t(3;3)), frequently associated with aberrant expression of EVI1, a gene that resides on 3q26.2. Secondly, we wished to elucidate why certain human AMLs showed high EVI1 expression without having chromosome 3q26 abnormalities. We investigated the importance high EVI1 levels in those leukemias and studied the potential to include EVI1 expression analysis in the diagnosis of AML. The data obtained from the last three chapters increase our understanding of the molecular and biological effects of EVI1 when aberrantly expressed in AML.

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