Background:
Imatinib mesylate is the first tyrosine kinase inhibitor approved
for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However,
previous studies have shown that about 20-30% of patients eventually would develop resistance
to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL
kinase domain mutation. One of the most common and serious variations account for
imatinib response is T315I of ABL1 gene.
Objective:
The study aimed to examine the association of T315I mutation with the ABL1
gene and its relation to major molecular response (MMR) achievement in CML patients.
This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different
possible variations in the ABL1 gene.
Methods:
This was a cross-sectional study on Indonesian CML patients in chronic phase.
We analyzed 120 blood samples from patients in chronic phase who have received
imatinib mesylate (IM) for ≥12 months.
Results:
There were no T315I, F311I, and F317L mutations found in this study. However,
we found another variation, which was 36 substitutions from A to G at position 163816 of
ABL1 gene (according to NG_012034.1).
Conclusions:
We found no T315I, F311I, and F317L mutations in this study. Our findings
suggest that there might be other factors that influenced the MMR achievement in our
study patients. However, there were 36 substitutions from A to G at position 163.816 (according
to NG_012034.1) that needed further examination to explore the significance of
this mutation in clinical practice.
Overcoming imatinib resistance conferred by the BIM deletion polymorphism in chronic myeloid leukemia with splice-switching antisense oligonucleotides
