Homogeneously staining region in anthracycline-resistant HL-60/AR cells not associated with MDR1 amplification.
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.
Gervasoni
J E
JE
Winthrop University Hospital, Division of Oncology/Hematology, Mineola, New York 11501.
Taub
R N
RN
Yu
M T
MT
Warburton
D
D
Sabbath
M
M
Gilleran
S
S
Coppock
D L
DL
D'Alessandri
J
J
Krishna
S
S
Rosado
M
M
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D015139:Blotting, Southern; D002897:Chromosomes, Human, Pair 7 / Q000502:physiology; D004273:DNA, Neoplasm / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D007942:Leukemia, Experimental / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm