PMID- 23355941
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130129
LR  - 20211021
IS  - 2038-8322 (Print)
IS  - 2038-8330 (Electronic)
IS  - 2038-8322 (Linking)
VI  - 4
IP  - 4
DP  - 2012 Nov 19
TI  - Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance 
      in Philadelphia chromosome positive Malaysian chronic myeloid leukemia patients.
PG  - e23
LID - 10.4081/hr.2012.e23 [doi]
LID - e23
AB  - 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 BCR-ABL 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 BCR-ABL 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.
FAU - Elias, Marjanu Hikmah
AU  - Elias MH
AD  - Human Genome Centre;
FAU - Baba, Abdul Aziz
AU  - Baba AA
FAU - Husin, Azlan
AU  - Husin A
FAU - Abdullah, Abu Dzarr
AU  - Abdullah AD
FAU - Hassan, Rosline
AU  - Hassan R
FAU - Sim, Goh Ai
AU  - Sim GA
FAU - Wahid, S Fadilah Abdul
AU  - Wahid SF
FAU - Ankathil, Ravindran
AU  - Ankathil R
LA  - eng
PT  - Journal Article
DEP - 20121123
PL  - Switzerland
TA  - Hematol Rep
JT  - Hematology reports
JID - 101556723
PMC - PMC3555211
OTO - NOTNLM
OT  - BCR-ABL dependent mechanisms
OT  - chronic myeloid leukemia
OT  - imatinib mesylate
OT  - mutation.
OT  - tyrosine kinase domain
COIS- Conflict of interests: the authors report no potential conflict of interests.
EDAT- 2013/01/29 06:00
MHDA- 2013/01/29 06:01
PMCR- 2012/11/23
CRDT- 2013/01/29 06:00
PHST- 2012/07/23 00:00 [received]
PHST- 2012/10/23 00:00 [revised]
PHST- 2012/10/31 00:00 [accepted]
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/01/29 06:01 [medline]
PHST- 2012/11/23 00:00 [pmc-release]
AID - hr.2012.e23 [pii]
AID - 10.4081/hr.2012.e23 [doi]
PST - ppublish
SO  - Hematol Rep. 2012 Nov 19;4(4):e23. doi: 10.4081/hr.2012.e23. Epub 2012 Nov 23.