Cancer drug resistance

STI-571 is an Abelson tyrosine kinase (Abl) inhibitor that is being tested in clinical trials to treat chronic myeloid leukemia (CML). A chromosomal translocation in CML patients results in production of the Bcr-Abl fusion protein, which is constitutively active and oncogenic. In the June 21 ScienceXpress, Gorre et al. report on the mechanism of relapse in STI-571 patients (Sciencexpress 2001, 10.1126/science.1062538). They found that patients in STI-571 remission had reactivated Bcr-Abl activity; 3 of the 11 patients had amplified copies of the oncogenic BCR-ABL gene. Two thirds of patients tested harboured a single point mutation within the ATP-binding site of Bcr-Abl. Thus the BCR-ABL gene appears important in both the initiation and the maintenance of tumorigenicity. Identifying mutated alleles may help to detect drug-resistant clones prior to clinical relapse.