2. Elucidating the functional role of nucleoporin Nup98 in acute myeloid leukaemia
Acute myeloid leukaemia (AML) is a disease characterised by uncontrolled proliferation of haematopoietic precursor cells often resulting in the disruption of normal haematopoiesis. Impaired differentiation of hematopoietic precursor cells are often associated with chromosomal translocations that involve the nucleoporin NUP98 fused to more than 20 different partner genes, including homeobox genes, such as HoxA9. Nup98-associated leukaemia are characterised by their aggressiveness and resistance to chemotherapy. Resistance to chemotherapy occurs frequently due to restored DNA repair pathways and consequently blocked senescence, differentiation and apoptosis. Our intention is to gradually dissect the mechanisms of NUP98-mediated cellular transformation.