High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance.

摘要: Point mutations were found in the adenosine triphosphate (ATP) binding region of BCR/ABL 12 18 patients with chronic myeloid leukemia (CML) or Ph-positive acute lymphoblastic (Ph(+) ALL) and imatinib resistance (defined as loss established hematologic response), but they only 1 10 CML refractoriness (failure to achieve cytogenetic response). In for whom samples available, mutation was not detected before initiation therapy. Three (T315I, Y253H, F317L present 3, 1, patients, respectively) have a predicted role abrogating BCR/ABL, whereas 3 other (E255K, G250E, M351T, 4, 2, 2 do not. Thus we confirm high frequency clustered within ATP-binding resistant patients. Screening may allow intervention relapse by identifying emerging defined impacts on binding. Certain respond higher doses imatinib, mandate switching another therapeutic strategy.