Immunity to chronic myelogenous leukemia

The advent of imatinib mesylate represents a paradigm of rational drug development arising from an understanding of the molecular basis of disease. Drugs targeting the metabolic pathways that are critical for the maintenance of the malignant phenotype are the subjects of intense research. Imatinib mesylate and its future analogs will induce cytogenetic remissions in most treated CML patients; however, with increasing use of imatinib, it is evident that resistance to tyrosine kinase inhibitors occurs and likely will become a more significant issue [8385]. Furthermore, molecular complete remissions, traditionally considered a prerequisite for cure in CML, occur in only 10% to 12% of patients. These findings suggest that alternative or complementary therapies will play an important role in the treatment of CML in the future. Most evidence indicates that immunotherapy-based strategies work best in minimal residual disease states, especially in light of evidence showing that CML cells are capable of killing CTLs. Given the high rate of cytogenetic responses to imatinib mesylate in CML, logical future treatment strategies will include combinations of tyrosine kinase inhibitors and immunotherapies such as vaccines. The rapidly increasing understanding of highly specific immune responses will lead to novel and improved immunotherapy strategies for CML patients. Such advances can be expected to revolutionize the field much the way that imatinib mesylate and other targeted small molecules have revolutionized our conception of traditional chemotherapy.