Selection pressure phenomenon during treatment of chronic myeloid leukemia patients with BCR-ABL1 tyrosine kinase inhibitors: problem analysis on the basis of case report

Abstract

Despite a great progress related to the introduction of tyrosine kinase inhibitors (TKI) to the therapy of patients with chronic myeloid leukemia (CML), resistance to the first-line treatment with imatinib (IM) is diagnosed in about 15% of patients. In about 40% of cases it is related to the presence of mutations affecting kinase domain of BCR-ABL1 (KD BCR-ABL1). Some defects are IM-resistant and its further administration leads to the selection of resistant clones, insensitive also to the 2nd generation TKIs (dasatinib, nilotinib). This paper focuses on medical history of patient diagnosed with CML in the chronic phase in whom nilotinib treatment was started due to the appearance of IM-resistance. Administration of nilotinib allowed to obtain major cytogenetic response and, subsequently, its loss due to the emergence of Y253H mutation within KD BCR-ABL1. Substitution of the 2nd generation drug to dasatinib allowed to obtain complete hematological response after 3 months of treatment. Unfortunately, the acceleration phase of the disease and the presence of another F317L mutation of KD BCR-ABL1 were documented thereafter. Disease outcome in the presented case was the reason for undertaking a discussion about selection pressure phenomenon related to TKI administration in patients with CML.
Hematologia 2010; 1, 3: 261-266