Elias, Marjanu Hikmah and Baba, Abdul Aziz and Husin, Azlan and Abdullah, Abu Dzarr and Hassan, Rosline and Goh, Ai Sim and Abdul Wahid, S. Fadilah and Ankathil, Ravindran
(2012)
Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients.
Hematology Reports, 4 (4).
pp. 86-90.
ISSN 2038-8322
Abstract
Development of resistance to imatinib
mesylate (IM) in chronic myeloid leukemia
(CML) patients is mediated by different mechanisms
that can be classified as BCR-ABL
dependent or BCR-ABL independent pathways.
BCR-ABL dependent mechanisms are most frequently
associated with point mutations in
tyrosine kinase domain (TKD) of BCR-ABL1
and also with BCR-ABL gene amplification.
Many different types and frequencies of mutations
have been reported in different studies,
probably due to the different composition of
study cohorts. Since no reports are available
from Malaysia, this study was undertaken to
investigate the frequency and pattern of BCRABL
kinase domain mutations using dHPLC
followed by sequencing, and also status of
BCR-ABL gene amplification using fluorescence
in situ hybridization (FISH) on 40 IM
resistant Malaysian CML patients. Mutations
were detected in 13 patients (32.5%). Five different
types of mutations (T315I, E255K,
Y253H, M351T, V289F) were identified in these
patients. In the remaining 27 IM resistant CML
patients, we investigated the contribution
made by BCR-ABL gene amplification, but
none of these patients showed amplification. It
is presumed that the mechanisms of resistance
in these 27 patients might be due to BCRABL
independent pathways. Different mutations
confer different levels of resistance and,
therefore, detection and characterization of
TKD mutations is highly important in order to
guide therapy in CML patients.
Actions (login required)
 |
View Item |
![[img]](http://eprints.usm.my/style/images/fileicons/application_pdf.png)
