Cytogenetic characterization of chromosomal rearrangement in a human vinblastine-resistant CEM cell line: use of comparative genomic hybridization and fluorescence in situ hybridization.
In order to identify genomic changes associated with drug-resistance acquisition, we performed R-banding karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization to compare a human T-cell lymphoblastic leukemia cell line, CEM-wild type, and a subline with resistance to vinblastine (CEM-VLB) and overexpressing P-glycoprotein. Comparative genomic hybridization analysis showed that the CEM-VLB cell line carried chemoresistance-associated chromosomal abnormalities (amplification of 7q11 approximately q22, losses of chromosomes 2, 3, 5, 9, 10, and 16, and deletion of 4q13 approximately qter). Fluorescence in situ hybridization identified an amplified 7q21 region translocated on the short arm of a chromosome 2. This region contained the MDR1 gene locus and probably neighboring genes, such as SRI or MDR3/ABCB4. According to previous reports, this chromosomal rearrangement occurred during drug selection and attested a resistance acquisition.
Struski
Stephanie
S
Laboratory of Hematology, Robert Debré Hospital and Medical Faculty (UPRES EA 20-70-IFR 53 Biomolecules), 51092, Reims Cedex, France. sstruski@chu-reims.fr
Cornillet-Lefebvre
Pascale
P
Doco-Fenzy
Martine
M
Dufer
Jean
J
Ulrich
Evelyne
E
Masson
Linda
L
Michel
Nicole
N
Gruson
Nadine
N
Potron
Gerard
G
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping / Q000379:methods; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping / Q000379:methods; D015458:Leukemia, T-Cell / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014747:Vinblastine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D014747:Vinblastine