Establishment of Inducible Expression Systems to Study the Role of STAT-Transcription Factors in AML

Acute myeloid leukemia (AML) is characterized by a clonal, malignant expansion of myeloid precursor cells. These cells are characterized by a block of differentiation. AML- blasts express cytokine receptors to which myeloid growth factors are binding and thus activate the JAK/STAT-signalling-pathway. In a subset of human cancers, including AML, and transformed cell lines STAT-proteins are persistently activated. Furthermore, STAT3 has transforming potential in epithelial cells in vitro and STAT5 is also involved in cellular transformation by the BCR-ABL oncogene. Recently it has been shown that STAT3 and STAT5 are also activated by transforming tyrosine-kinases in acute leukemias (TEL- JAK2, FLT3-ITD, TEL-ABL). The aim of this project is to further elucidate the functional role of STATs in AML.