ABSTRACT
This chapter reviews central role of Bcr-Abl in Chronic Myeloid Leukemia (CML) pathogenesis, the development of tyrosine kinase inhibitors against Bcr-Abl, and how this pairing of a crucial target with specific and evolving inhibitors has been a paradigm for unprecedented success. Kinase domain mutations may thus represent a natural element of CML disease progression that may be highlighted by selection pressure with the use of potent Abelson kinase inhibitors. Bcr-Abl is central and well suited as a target for therapy in CML. Using classic karyotyping, the Ph chromosome abnormality can be detected in approximately 90% of patients with CML. Investigation of CML cases with relapsing disease queried for potential reasons for the reactivation of the kinase. Several important experimental works established the ability of Bcr-Abl, as a singular oncogenic abnormality, to cause leukemia. An inhibitor of the Bcr-Abl kinase for Ph(+) leukemias would thus be a rational choice and predicted to be effective and selective therapy.
