Mechanisms of drug resistance in human leukemia.

Drug resistance remains a major obstacle to cure of patients with acute leukemia. At the present time, most centers are reporting 90% complete remission rates in acute lymphatic leukemia (ALL) and 70%-80% complete remission rates in patients with acute nonlymphocytic leukemia (ANLL). However, 5-year disease-free survival rates are only 50% and 10%-15%, respectively, in these diseases. This is almost certainly due to the development of drug resistance even to the combination chemotherapy programs utilized to treat these diseases [1]. In this paper, we review the mechanisms by which cells become resistant to methotrexate (MTX) and strategies to eradicate selectively leukemic cells that have acquired resistance to the drug.