Chronic myeloid leukaemia : from molecular genetics to therapeutic approaches

The BCR-ABL fusion gene is both a marker of the disease and one of the causal events in the disease itself. This work will deal with both properties of the gene in chronic phase CML. The mechanisms underlying the acute transformation (acquisitions of new oncogenic changes) could be the matter of another thesis, but will not be discussed in the present work, since I did not work on this subject. In the second and third chapters, I will present data about the use of molecular genetics as a tool for diagnosis, prognosis and follow-up if CML patients. Part of chapter II will also be devoted to some aspects of the mechanisms underlying the generation of the hybrid messenger RNA. The fourth chapter will present preliminary data from ongoing work: the use of antisense molecules to inhibit the expression of the fused ongoing BCR-ABL transcript. This latte part is based upon the evidence that P210 is a causal event in the course of the disorder; if one could inhibit the expression of the abnormal protein, one might have new therapeutic tools, specific for the malignant cells