Vol 1, No 3 (2010)
Case report
Published online: 2010-07-27
Selection pressure phenomenon during treatment of chronic myeloid leukemia patients with BCR-ABL1 tyrosine kinase inhibitors: problem analysis on the basis of case report
Hematologia 2010;1(3):261-266.
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
Hematologia 2010; 1, 3: 261-266
Keywords: chronic myeloid leukemiaBCR-ABL1 tyrosine kinase inhibitorsclonal selectionselection pressuresequential therapy