The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level
Chronic myelogenous leukemia (CML) is an uncommon but fatal cancer. More than 95 percent of patients afflicted with this malignancy have a chromosomal abnormality known as the Philadelphia chromosome. This genetic mutation is characterized by a swap of genetic matter between two different chromosomes so that a single chromosome (number 22) has a piece missing. The mutated chromosome codes for an enzyme—tyrosine kinase—that is hyperactive and ramps up production of white blood cells that leads to leukemia. A chemical compound was identified that selectively targets the kinase protein. Gleevec was FDA approved in 2001, and the results have been quite impressive. It outperformed the existing first-line treatment for CML. It is safer than a bone marrow transplant. Gleevec is unique among cancer drugs because it is taken orally (instead of administered intravenously) at home (instead of the hospital or clinic) with very manageable side effects. Science writer Wapner has pieced together a detailed account of a spectacular scientific success story and a turning point in the treatment of cancer. --Tony Miksanek