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Characterization of the biological and molecular effects of the PML-RARalfa oncogene in the initiation of leukemogenesis : phd degree in molecular medicine : tesi di dottorato

Cambiaghi, Valeria

Tesi o dissertazioni - 2008

Valeria Cambiaghi n. matr. R05706 Abstract Acute Promyelocytic Leukemia (APL) is a rare disorder which accounts for ~10% of the human myeloid leukemias, characterized by the expression of the PML-RARa fusion protein (t(15;17)). Expression of the fusion protein hematopoietic stem cells (HSCs) is sufficient to initiate leukemogenesis in mice. The biological activities of PML-RARa have been extensively investigated in vitro. Ectopic expression of the fusion protein in progenitor cells induces the block of terminal differentiation and increases cell survival. However, the in vivo properties of PML-RARa are yet unknown. The general aim of my thesis project was to define the in vivo biological activities of the PML-RARa oncogene and, specifically, to determine whether it induces genomic instability. As model system, I studied the bone marrow of PML-RARa transgenic mice prior to the development of leukemias (pre-leukemic bone marrow). I have demonstrated that PML-RARa expression favours the expansion of HSCs when they are induced to hyper-proliferate under stress conditions [...]
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