| A subset of the leukaemic clone, the leukaemic stem cell (L-HSC), is responsible for the maintenance and propagation of a leukaemia. Most current therapies, however, do not target this population. In this thesis, I show that a determinant of disease phenotype is the frequency of the leukaemic stem cell within the leukaemic population. Moreover, the frequency of L-HSC in a leukaemia is predetermined by the inherent properties of the cell that is transformed and can be attributed to the ontogenic origin of the cell. Ideal therapies would specifically target mechanistic defects in leukaemic stem cells; however, the pathways that are involved and what oncogenic defects can be targeted for therapy remain to be discovered. As it is not known if all oncogenes can be targeted or what the determinants of oncogenic dependency are, I have developed a system to further elucidate this as described herein. |
