PMID- 14653203
OWN - NLM
STAT- MEDLINE
DCOM- 20040224
LR  - 20151119
IS  - 0047-1860 (Print)
IS  - 0047-1860 (Linking)
VI  - 51
IP  - 10
DP  - 2003 Oct
TI  - [The monitoring of residual disease for chronic myelogenous leukemia patients 
      treated with imatinib mesylate: detection of T315I mutation in ATP binding site 
      of BCR/ABL gene].
PG  - 1023-9
AB  - Imatinib Mesylate, a specific inhibitor of BCR/ABL tyrosine kinase, was developed 
      as a molecularly targeted drug for the treatment of patients with chronic 
      myelogenous leukemia. We evaluated effectiveness of the drug on cytogenetic 
      response for monitoring residual disease using fluorescence in situ 
      hybridization(FISH), reverse transcription-nested-polymerase chain 
      reaction(RT-nested-PCR) and competitive PCR strategy. Of 9 patients in chronic 
      phase, 7 achieved major cytogenetic response(CR) and 2 achieved minor CR by FISH. 
      In 3 out of 6 patients with complete CR, no BCR/ABL gene was detected by 
      RT-nested-PCR in peripheral blood or bone marrow specimens. Of 4 patients in 
      accelerated phase, 1 achieved complete CR but 3 developed blast crisis. Despite 
      high efficacy of Imatinib, 5 out of 13 patients showed resistance to the drug. To 
      clarify the mechanism of resistance, we have newly developed a method for 
      investigating a point mutation of T315I in tyrosine kinase domain of BCR/ABL gene 
      using RT-PCR restriction digested analysis. None of them showed T315I mutation. 
      The sensitivity of the method was as low as 10 copies of mutant gene. The method 
      is useful for screening the mutation when there are many clinical samples or low 
      copy number of BCR/ABL gene. BCR/ABL value obtained by FISH was of use to predict 
      cytogenetic response when residual disease was above 2 to 3%. Below this level, 
      the routine use of RT-nested-PCR was suffices to monitor minimal residual 
      disease.
FAU - Miyanishi, Setsuko
AU  - Miyanishi S
AD  - Tenri Institute of Medical Research, Tenri 632-8552.
FAU - Umeki, Kazumi
AU  - Umeki K
FAU - Hayashi, Takamasa
AU  - Hayashi T
FAU - Fukutsuka, Katsuhiro
AU  - Fukutsuka K
FAU - Okumura, Atsuko
AU  - Okumura A
FAU - Kishimori, Chiyuki
AU  - Kishimori C
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PL  - Japan
TA  - Rinsho Byori
JT  - Rinsho byori. The Japanese journal of clinical pathology
JID - 2984781R
RN  - 0 (Benzamides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Adult
MH  - Aged
MH  - Benzamides
MH  - Binding Sites/genetics
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Female
MH  - Fusion Proteins, bcr-abl
MH  - Humans
MH  - Imatinib Mesylate
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*diagnosis/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm, Residual/diagnosis/genetics
MH  - Piperazines/*therapeutic use
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors/*genetics
MH  - Pyrimidines/*therapeutic use
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2003/12/05 05:00
MHDA- 2004/02/26 05:00
CRDT- 2003/12/05 05:00
PHST- 2003/12/05 05:00 [pubmed]
PHST- 2004/02/26 05:00 [medline]
PHST- 2003/12/05 05:00 [entrez]
PST - ppublish
SO  - Rinsho Byori. 2003 Oct;51(10):1023-9.