Chronic Myelogenous Leukemia (CML) is a cancer of the white blood cells that is most commonly found in adults and in the elderly. Its incidence has been estimated to be 1 to 2 in 100,000 people. CML was the first cancer to be associated with a genetic abnormality, known as the Philadelphia Chromosome, which 95% of all CML patients carry in their cells.
The Philadelphia Chromosome is formed by exchanges of material belonging to two distinct chromosomes, number 9 and number 22. To form the Philadelphia Chromosome, these two chromosomes break at very specific places, disrupting the BCR (in chromosome 22) and the ABL (in chromosome 9) genes that were otherwise normal. Juxtaposition of these two genes in the Philadelphia Chromosome creates an abnormal kinase tyrosine known as BCR/ABL, which is an enzyme associated with cell regulation. The Philadelphia Chromosome is associated with loss of cell control and presence of immortal cells, which leads to cancer.
In the 1990s, ST1-571 (known as imatinib or Gleevec), a new inhibitor of kinase tyrosine, was developed and tested against CML cells. Since then, the drug has been used as the first line of treatment in many patients, increasing survival rates and improving patients' quality of life. However, some patients develop resistance to the drug, which has fostered development of novel drugs that act on alternative sites on the BCR/ABL enzyme.