Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome

The BCR-ABL tyrosine kinase, the product of the chimeric gene produced by the Philadelphia (Ph) chromosome, is the molecular abnormality that causes chronic myeloid leukemia (CML). During the chronic phase of the disease, there is massive clonal expansion of myeloid cells, which retain the ability to differentiate. Over time, however, the leukemic clone loses this ability, and the disease inevitably progresses to an acute leukemia known as blast crisis.1,2 In two thirds of patients the blasts are myeloid, and in one third they are lymphoid. Up to 20 percent of adults and 5 percent of children with acute lymphoblastic . . .