This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yanovich, S. Articles by Gewirtz, D. A. Search for Related Content PubMed PubMed Citation Articles by Yanovich, S. Articles by Gewirtz, D. A.

Characterization of a K562 Multidrug-resistant Cell Line¹

Departments of Medicine and Pharmacology, Medical College of Virginia, Richmond, Virginia 23298

A daunorubicin-resistant variant of the K562 human leukemia cell line (K562-R), which demonstrates cross-resistance to other anthracycline antibiotics and Vinca alkaloids, has been developed in vitro by continuous exposure to daunorubicin. Cross-resistance to anthracyclines and Vinca alkaloids is reversed when cells are exposed to drugs in the presence of verapamil, a calcium channel blocker. The K562-R cell line overexpresses a 4.5-kilobase mRNA, which is thought to code for the M_r 170,000 membrane glycoprotein associated with multidrug resistance. Transport studies indicate reduced intracellular accumulation and retention of daunorubicin in the K562-R cells as compared to the parent cell line. These studies further suggest the presence of distinct cellular pools composed of both rapidly and slowly exchanging drug, with the rapidly exchanging pool being more pronounced in the resistant line. The development of multidrug resistance in the K562-R cell line is also associated with the overexpression of five different cell surface membrane proteins ranging in molecular weight between 50,000 and 210,000, whose function remains to be defined.

¹ This work was supported by a grant from the ACS (CH-346).

² To whom requests for reprints should be addressed.

Received 3/11/88. Revised 10/17/88. Revised 3/20/89. Accepted 5/19/89.

This article has been cited by other articles:

				L. M. Greene, L. Kelly, V. Onnis, G. Campiani, M. Lawler, D. C. Williams, and D. M. Zisterer STI-571 (Imatinib Mesylate) Enhances the Apoptotic Efficacy of Pyrrolo-1,5-Benzoxazepine-6, a Novel Microtubule-Targeting Agent, in Both STI-571-Sensitive and -Resistant Bcr-Abl-Positive Human Chronic Myeloid Leukemia Cells J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 288 - 297. [Abstract] [Full Text] [PDF]

				C. Yu, M. Rahmani, J. Almenara, M. Subler, G. Krystal, D. Conrad, L. Varticovski, P. Dent, and S. Grant Histone Deacetylase Inhibitors Promote STI571-mediated Apoptosis in STI571-sensitive and -resistant Bcr/Abl+ Human Myeloid Leukemia Cells Cancer Res., May 1, 2003; 63(9): 2118 - 2126. [Abstract] [Full Text] [PDF]

				C. Yu, G. Krystal, P. Dent, and S. Grant Flavopiridol Potentiates STI571-induced Mitochondrial Damage and Apoptosis in BCR-ABL-positive Human Leukemia Cells Clin. Cancer Res., September 1, 2002; 8(9): 2976 - 2984. [Abstract] [Full Text] [PDF]

				C. Yu, G. Krystal, L. Varticovksi, R. McKinstry, M. Rahmani, P. Dent, and S. Grant Pharmacologic Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase/Mitogen-activated Protein Kinase Inhibitors Interact Synergistically with STI571 to Induce Apoptosis in Bcr/Abl-expressing Human Leukemia Cells Cancer Res., January 1, 2002; 62(1): 188 - 199. [Abstract] [Full Text] [PDF]

				M. Murata, I. Tamai, H. Kato, O. Nagata, H. Kato, and A. Tsuji Efflux Transport of a New Quinolone Antibacterial Agent, HSR-903, across the Blood-Brain Barrier J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 51 - 57. [Abstract] [Full Text]