Translation of the Philadelphia chromosome into therapy for CML

Throughout its history, chronic myeloid leukemia (CML) has set precedents for cancer research and therapy. These range from the identification of the first specific chromosomal abnormality associated with cancer to the development of ima-tinib as a specific, targeted therapy for the disease. The successful development of imatinib as a therapeutic agent for CML can be attributed directly to decades of scientific discoveries. These discoveries determined that the BCR-ABL tyrosine kinase is the critical pathogenetic event in CML and an ideal target for therapy. This was confirmed in clinical trials of imatinib, with imatinib significantly im-proving the long-term survival of patients with CML. Continuing in this tradition of scientific discoveries leading to improved therapies, the understanding of resis-tance to imatinib has rapidly led to strate-gies to circumvent resistance. Continued studies of hematologic malignancies will allow this paradigm of targeting molecu-lar pathogenetic events to be applied to many additional hematologic cancers. (Blood. 2008;112:4808-4817