Chronic myeloid leukemia (CML) is a clonal stem-cell disorder in which the reciprocal translocation t(9;22) generates two novel fusion genes: BCR-ABL on the derivative 22q– (Philadelphia) chromosome, and ABL-BCR on chromosome 9q+. The ABL gene product is a protein tyrosine kinase, and the fusion protein BCR-ABL has constitutive kinase activity that deregulates signal transduction pathways, causing abnormal cell cycling, inhibition of apoptosis, and increased proliferation of cells. The natural course of the disease is usually characterized by three sequential phases (the chronic, accelerated, and blast-crisis phases), during which there is progressively more resistance to therapy.

Interferon alfa therapy extends survival . . .