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STAT3 and STAT5 signaling in normal and leukemic hematopoietic cells

(2010) Wierenga, Albertus Titus Johannes

The formation of blood cells is a strictly regulated process termed hematopoiesis. Adult blood cells are formed from hematopoietic stem cells by means of proliferation and differentiation. These processes are regulated in the cell by certain proteins that regulate the expression of certain genes. An important group of proteins involved in these processes is the family of STAT proteins. The studies in this thesis describe different aspects of the proteins STAT3 and STAT5. It is described how STAT3 can be continuously activated in blood cells of patients with Acute Myeloid Leukemia. Besides this, the effects of a compound that exerts negative effects on the cell growth, called Transforming Growth Factor beta1 was investigated. For maximal activation of STAT3, phosphorylation on amino acid serine727 is important and the involved mechanism was studied in this thesis. Subsequently, it is described how STAT5 can affect the growth and differentiation of blood cells. STAT5 can be activated at different levels and it was found that this imposes different phenotypes on the cells. Eventually it became clear that the effects of STAT5 could be dissected in effects on the differentiation and on the proliferation. In summary, it can be concluded that STAT3 and STAT5 are important proteins and that gaining more insight in the properties of these proteins can contribute to the understanding of blood cell formation and the mechanisms behind the evolution of leukemia.

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