Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients
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 t...
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| Format: | Article |
| Language: | English |
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PAGEpress
2012
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| Online Access: | http://eprints.usm.my/38527/ http://eprints.usm.my/38527/1/Contribution_of_BCR-ABL_kinase_domain_mutations_to_imatinib_mesylate_resistance_in_Philadelphia_chromosome.pdf |
| _version_ | 1848878494515200000 |
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| author | Elias, Marjanu Hikmah Baba, Abdul Aziz Husin, Azlan Abdullah, Abu Dzarr Hassan, Rosline Goh, Ai Sim Abdul Wahid, S. Fadilah Ankathil, Ravindran |
| author_facet | Elias, Marjanu Hikmah Baba, Abdul Aziz Husin, Azlan Abdullah, Abu Dzarr Hassan, Rosline Goh, Ai Sim Abdul Wahid, S. Fadilah Ankathil, Ravindran |
| author_sort | Elias, Marjanu Hikmah |
| building | USM Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T17:32:14Z |
| format | Article |
| id | usm-38527 |
| institution | Universiti Sains Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T17:32:14Z |
| publishDate | 2012 |
| publisher | PAGEpress |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | usm-385272018-01-24T04:09:09Z http://eprints.usm.my/38527/ Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients Elias, Marjanu Hikmah Baba, Abdul Aziz Husin, Azlan Abdullah, Abu Dzarr Hassan, Rosline Goh, Ai Sim Abdul Wahid, S. Fadilah Ankathil, Ravindran R5-920 Medicine (General) 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. PAGEpress 2012-11 Article PeerReviewed application/pdf en http://eprints.usm.my/38527/1/Contribution_of_BCR-ABL_kinase_domain_mutations_to_imatinib_mesylate_resistance_in_Philadelphia_chromosome.pdf 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3555211/ |
| spellingShingle | R5-920 Medicine (General) Elias, Marjanu Hikmah Baba, Abdul Aziz Husin, Azlan Abdullah, Abu Dzarr Hassan, Rosline Goh, Ai Sim Abdul Wahid, S. Fadilah Ankathil, Ravindran Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients |
| title | Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients |
| title_full | Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients |
| title_fullStr | Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients |
| title_full_unstemmed | Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients |
| title_short | Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients |
| title_sort | contribution of bcr-abl kinase domain mutations to imatinib mesylate resistance in philadelphia chromosome positive malaysian chronic myeloid leukemia patients |
| topic | R5-920 Medicine (General) |
| url | http://eprints.usm.my/38527/ http://eprints.usm.my/38527/ http://eprints.usm.my/38527/1/Contribution_of_BCR-ABL_kinase_domain_mutations_to_imatinib_mesylate_resistance_in_Philadelphia_chromosome.pdf |