Monitoring response and resistance to treatment in chronic myeloid leukemia

Abstract

Chronic myeloid leukemia (cml) results from expression of the constitutive tyrosine kinase activity of the Bcr-Abl oncoprotein. Imatinib, a tyrosine kinase inhibitor (tki), is highly effective in the treatment of cml. However, some patients treated with imatinib will fail to respond, will respond suboptimally, or will relapse because of primary or acquired resistance or intolerance. Research activities focusing on the mechanisms that underlie imatinib resistance have identified mutations in the BCR-ABL gene, clonal evolution, and amplification of the BCR-ABL gene as common causes. Cytogenetic and molecular techniques are currently used to monitor cml therapy for both response and relapse. With multiple and more potent therapeutic options now available, monitoring techniques can permit treatment to be tailored to the individual patient based on disease characteristics-for example, according to BCR-ABL mutation profile or to patient characteristics such as certain comorbid conditions. This approach should benefit patients by increasing the potential for better long-term outcomes.

Keywords: Chronic myeloid leukemia; drug monitoring; drug resistance; imatinib; protein kinase inhibitors.

FIGURE 1

Algorithm for chronic myeloid leukemia (cml) treatment (adapted from Baccarani 16). cp = chronic phase; tki = tyrosine kinase inhibitor; Allo-sct = allogeneic stem cell transplantation.