PMID- 33361712
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20211004
IS  - 0126-8635 (Print)
IS  - 0126-8635 (Linking)
VI  - 42
IP  - 3
DP  - 2020 Dec
TI  - Clinical implications of conventional cytogenetics, fluorescence in situ 
      hybridization (FISH) and molecular testing in chronic myeloid leukaemia patients 
      in the tyrosine kinase inhibitor era - A review.
PG  - 307-321
AB  - Chronic myeloid leukaemia (CML) provides an illustrative disease model for both 
      molecular pathogenesis of cancer and rational drug therapy. Imatinib mesylate 
      (IM), a BCR-ABL1 targeted tyrosine kinase inhibitor (TKI) drug, is the first line 
      gold standard drug for CML treatment. Conventional cytogenetic analysis (CCA) can 
      identify the standard and variant Philadelphia (Ph) chromosome, and any 
      additional complex chromosome abnormalities at diagnosis as well as during 
      treatment course. Fluorescence in situ hybridization (FISH) is especially 
      important for cells of CML patients with inadequate or inferior quality 
      metaphases or those with variant Ph translocations. CCA in conjunction with FISH 
      can serve as powerful tools in all phases of CML including the diagnosis, 
      prognosis, risk stratification and monitoring of cytogenetic responses to 
      treatment. Molecular techniques such as reverse transcriptase-polymerase chain 
      reaction (RT-PCR) is used for the detection of BCR-ABL1 transcripts at diagnosis 
      whereas quantitative reverse transcriptase-polymerase chain reaction (qRTPCR) is 
      used at the time of diagnosis as well as during TKI therapy for the quantitation 
      of BCR-ABL1 transcripts to evaluate the molecular response and minimal residual 
      disease (MRD). Despite the excellent treatment results obtained after the 
      introduction of TKI drugs, especially Imatinib mesylate (IM), resistance to TKIs 
      develops in approximately 35% - 40% of CML patients on TKI therapy. Since point 
      mutations in BCR-ABL1 are a common cause of IM resistance, mutation analysis is 
      important in IM resistant patients. Mutations are reliably detected by nested PCR 
      amplification of the translocated ABL1 kinase domain followed by direct 
      sequencing of the entire amplified kinase domain. The objective of this review is 
      to highlight the importance of regular and timely CCA, FISH analysis and 
      molecular testing in the diagnosis, prognosis, assessment of therapeutic 
      efficacy, evaluation of MRD and in the detection of BCR-ABL1 kinase mutations 
      which cause therapeutic resistance in adult CML patients.
FAU - Ankathil, R
AU  - Ankathil R
AD  - Human Genome Centre, School of Medical Sciences, Health campus, Universiti Sains 
      Malaysia, 16150 Kubang kerian, Kelantan, Malaysia. rankathil@hotmail.com.
FAU - Ismail, S M
AU  - Ismail SM
FAU - Mohd Yunus, N
AU  - Mohd Yunus N
FAU - Sulong, S
AU  - Sulong S
FAU - Husin, A
AU  - Husin A
FAU - Abdullah, A D
AU  - Abdullah AD
FAU - Hassan, R
AU  - Hassan R
LA  - eng
PT  - Journal Article
PL  - Malaysia
TA  - Malays J Pathol
JT  - The Malaysian journal of pathology
JID - 8101177
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Antineoplastic Agents/therapeutic use
MH  - Cytogenetic Analysis/*methods
MH  - Drug Resistance, Neoplasm/genetics
MH  - Fusion Proteins, bcr-abl/*analysis/genetics
MH  - Humans
MH  - Imatinib Mesylate/therapeutic use
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/*genetics
MH  - Molecular Targeted Therapy/*methods
MH  - Mutation
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Reverse Transcriptase Polymerase Chain Reaction/*methods
EDAT- 2020/12/29 06:00
MHDA- 2021/10/05 06:00
CRDT- 2020/12/28 11:44
PHST- 2020/12/28 11:44 [entrez]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PST - ppublish
SO  - Malays J Pathol. 2020 Dec;42(3):307-321.