PMID- 12716468
OWN - NLM
STAT- MEDLINE
DCOM- 20030820
LR  - 20190513
IS  - 0910-5050 (Print)
IS  - 1876-4673 (Electronic)
IS  - 0910-5050 (Linking)
VI  - 93
IP  - 8
DP  - 2002 Aug
TI  - Molecular cytogenetic characterization of drug-resistant leukemia cell lines by 
      comparative genomic hybridization and fluorescence in situ hybridization.
PG  - 902-10
AB  - Resistance to chemotherapeutic drugs is one of the major difficulties encountered 
      during cancer chemotherapy. To detect genomic aberrations underlying the acquired 
      drug resistance, we examined three cultured human myelomonocytic leukemia cell 
      sublines each resistant to adriamycin (ADR), 1-beta-1-D-arabinofuranosylcytosine 
      (ara-C), or vincristine (VCR), using comparative genomic hybridization (CGH), 
      fluorescence in situ hybridization (FISH), RT-PCR, and western blot techniques. 
      Chromosomes 7, 10 and 16 most conspicuously showed frequent aberrations among the 
      resistant sublines as compared to the parental KY-821 cell line. In ADR-resistant 
      cells, gains at 7q21, 16p12, 16p13.1-13.3, 16q11.1-q12.1, and losses at 
      7p22-pter, 7q36-qter, 10p12, 10p11.2-pter, 10q21-q25, 10q26-qter were notable. In 
      ara-C-resistant cells, no remarkable gain or loss on chromosome 7, but losses at 
      10p14-pter, 10q26-qter and 16p11.2-p11.3 were observed. In VCR-resistant cells, 
      gain at 7q21 and losses at 10p11-p13, 10p15 and 16p11.2-p13.3 were found. FISH 
      identified amplified signals for the MDR-1 gene located at 7q21.1 in ADR- and 
      VCR- but not ara-C-resistant cells, and for the MRP-1 gene located at 16p13.1 in 
      ADR-resistant cells. These findings were validated at the mRNA and protein 
      levels. Overlapping of the amplified MRP-1 gene with MDR-1 gene may play a 
      critical part in the acquisition of resistance to ADR. Resistance to ara-C 
      excluded MDR-1 gene involvement and highlighted other key genes such as MXR gene. 
      Several other genes putatively involved in the development of drug resistance 
      might lie in other aberrated chromosomal regions.
FAU - Shimizu, Hajime
AU  - Shimizu H
AD  - The Department of Molecular Pathology, Institute of Gerontology, Nippon Medical 
      School, Nakahara-ku, Kawasaki 211-8533, Japan.
FAU - Fukuda, Takeaki
AU  - Fukuda T
FAU - Ghazizadeh, Mohammad
AU  - Ghazizadeh M
FAU - Nagashima, Mikio
AU  - Nagashima M
FAU - Kawanami, Oichi
AU  - Kawanami O
FAU - Suzuki, Toshimitsu
AU  - Suzuki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Jpn J Cancer Res
JT  - Japanese journal of cancer research : Gann
JID - 8509412
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 04079A1RDZ (Cytarabine)
RN  - 5J49Q6B70F (Vincristine)
RN  - 80168379AG (Doxorubicin)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - Antimetabolites, Antineoplastic/pharmacology
MH  - Antineoplastic Agents/pharmacology
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Blotting, Western
MH  - Cell Nucleus/metabolism
MH  - Chromosome Mapping
MH  - Cytarabine/pharmacology
MH  - Doxorubicin/pharmacology
MH  - *Drug Resistance, Neoplasm
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Inhibitory Concentration 50
MH  - Leukemia/*genetics/metabolism
MH  - Multidrug Resistance-Associated Proteins/metabolism
MH  - Nucleic Acid Hybridization
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
MH  - Vincristine/pharmacology
PMC - PMC5927113
EDAT- 2003/04/30 05:00
MHDA- 2003/08/21 05:00
PMCR- 2002/08/01
CRDT- 2003/04/30 05:00
PHST- 2003/04/30 05:00 [pubmed]
PHST- 2003/08/21 05:00 [medline]
PHST- 2003/04/30 05:00 [entrez]
PHST- 2002/08/01 00:00 [pmc-release]
AID - CAE902 [pii]
AID - 10.1111/j.1349-7006.2002.tb01336.x [doi]
PST - ppublish
SO  - Jpn J Cancer Res. 2002 Aug;93(8):902-10. doi: 10.1111/j.1349-7006.2002.tb01336.x.