Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia

Imatinib, an inhibitor of the mutant tyrosine kinase that causes chronic myeloid leukemia (CML), is effective in patients with chronic-phase CML who have no response to the standard treatment, interferon alfa. In this study of 1106 patients with previously untreated chronic-phase CML, imatinib was superior to a combination of interferon alfa and cytarabine as initial therapy. In a study of 1106 patients, imatinib was superior to interferon alfa plus cytarabine as initial therapy. The Philadelphia chromosome (Ph), 1 the result of a t(9;22) reciprocal translocation, 2 is present in over 90 percent of patients with chronic myeloid leukemia (CML) and results in the juxtaposition of DNA sequences from the BCR and ABL genes. 3 – 6 BCR-ABL encodes a protein, p210BCR-ABL, with dysregulated tyrosine kinase activity, 7 which is necessary and sufficient for leukemogenesis. 8 – 11 Imatinib mesylate (Gleevec, Novartis), a potent competitive inhibitor of the tyrosine kinases associated with ABL, 12 , 13 C-KIT, 14 , 15 platelet-derived growth factor receptor, 13 , 14 , 16 and ARG, 17 impedes the interaction of ATP with these proteins 18 and thereby inhibits their ability to phosphorylate and activate . . .