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∼q22, losses of chromosomes 2, 3, 5, 9, 10, and 16, and deletion of 4q13∼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.