1. Homogeneously staining region in anthracycline-resistant HL-60/AR cells not associated with MDR1 amplification.
- Author
-
Gervasoni JE Jr, Taub RN, Yu MT, Warburton D, Sabbath M, Gilleran S, Coppock DL, D'Alessandri J, Krishna S, and Rosado M
- Subjects
- Base Sequence, Blotting, Southern, Chromosomes, Human, Pair 7 physiology, DNA, Neoplasm genetics, Gene Amplification genetics, Gene Expression genetics, Humans, Karyotyping, Molecular Sequence Data, RNA, Messenger genetics, RNA, Neoplasm genetics, Antibiotics, Antineoplastic pharmacology, Drug Resistance genetics, Leukemia, Experimental genetics, Leukemia, Myeloid genetics
- Abstract
Anthracycline-resistant HL-60/AR cells and their drug-sensitive HL-60/S counterparts were characterized by karyotypic analysis and examined for the overexpression of DNA and mRNA sequences coding for P-glycoprotein (Pgp). The HL-60/S cells were karyotypically stable over a 5-year period of study (1986-1991), except for an additional small Giemsa-positive band noted at 7q22 in cultures harvested in 1987, but not in 1986. This change did not affect drug sensitivity. The drug-resistant HL-60/AR cells examined in 1986, 1987, and 1991 demonstrated a very stable karyotype. The most striking feature was a large homogeneously staining region in the long arm of chromosome 7 (7q11.2), and translocation of the remainder of the long arm to another centromere. Other changes in the HL-60/AR cells included inversion in 9q, partial deletion of the short arm of chromosome 10p, addition of material to the p arm of der(16), loss of chromosome 22, and the appearance of a new marker chromosome. Both HL-60/S and the HL-60/AR cells were found not to amplify DNA or mRNA sequences coding for the Pgp. Thus, although the HL-60/AR cells possess the classical multidrug resistance phenotype and demonstrate a homogeneously staining region near the region of the MDR1 gene, their resistance is due to mechanisms other than those coded for by MDR1.
- Published
- 1992