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Etoposide-induced DNA strand breaks in relation to p-glycoprotein and topoisomerase II protein expression in leukaemic cells from patients with AML and CLL.
Br J Haematol. 1999 May; 105(2):420-7.BJ

Abstract

Elevated expression of the membrane transporter p-glycoprotein (pgp) and impaired expression of the nuclear enzyme topoisomerase II (topo II) are well-known mechanisms for in vitro acquired drug resistance. The clinical relevance of topo II remains unclear, whereas a relationship between pgp levels and treatment results has been shown in acute myelogenous leukaemia (AML). We have investigated the relationships between the levels of topo II and pgp, and in vitro sensitivity to etoposide in mononuclear blood cells from 24 patients with AML, 16 with chronic lymphocytic leukaemia (CLL) and five healthy blood donors. Following incubation with etoposide, AML cells showed more DNA damage, determined by a DNA unwinding technique, than CLL cells (P = 0.001), whereas there was no difference in cellular etoposide accumulation. Pgp and topo IIbeta levels, determined by Western blot, showed a pronounced variation between patients, but no correlation with induced DNA damage, whereas topo IIalpha protein was undetectable. In the AML group, topo IIbeta expression correlated with pgp expression (rho = 0.7, P = 0.001, n = 24). The topo IIbeta expression was 147.4(+/-74.6)% in the pgp+ AML cells (n = 10), compared to 33.4(+/-27.8)% in pgp- AML cells (n = 14) (P = 0.0001). Our results show a previously unknown coexpression of topo IIbeta and pgp in AML, thereby suggesting that topo IIbeta is a potentially interesting resistance factor in AML.

Authors+Show Affiliations

Oncology-Pathology at Radiumhemme, Karolinska Institute and Hospital, Stockholm, Sweden. rong.zhou@cck.ki.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10233413

Citation

Zhou, R, et al. "Etoposide-induced DNA Strand Breaks in Relation to P-glycoprotein and Topoisomerase II Protein Expression in Leukaemic Cells From Patients With AML and CLL." British Journal of Haematology, vol. 105, no. 2, 1999, pp. 420-7.
Zhou R, Vitols S, Gruber A, et al. Etoposide-induced DNA strand breaks in relation to p-glycoprotein and topoisomerase II protein expression in leukaemic cells from patients with AML and CLL. Br J Haematol. 1999;105(2):420-7.
Zhou, R., Vitols, S., Gruber, A., Liliemark, J., Wang, Y., & Liliemark, E. (1999). Etoposide-induced DNA strand breaks in relation to p-glycoprotein and topoisomerase II protein expression in leukaemic cells from patients with AML and CLL. British Journal of Haematology, 105(2), 420-7.
Zhou R, et al. Etoposide-induced DNA Strand Breaks in Relation to P-glycoprotein and Topoisomerase II Protein Expression in Leukaemic Cells From Patients With AML and CLL. Br J Haematol. 1999;105(2):420-7. PubMed PMID: 10233413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Etoposide-induced DNA strand breaks in relation to p-glycoprotein and topoisomerase II protein expression in leukaemic cells from patients with AML and CLL. AU - Zhou,R, AU - Vitols,S, AU - Gruber,A, AU - Liliemark,J, AU - Wang,Y, AU - Liliemark,E, PY - 1999/5/8/pubmed PY - 1999/5/8/medline PY - 1999/5/8/entrez SP - 420 EP - 7 JF - British journal of haematology JO - Br J Haematol VL - 105 IS - 2 N2 - Elevated expression of the membrane transporter p-glycoprotein (pgp) and impaired expression of the nuclear enzyme topoisomerase II (topo II) are well-known mechanisms for in vitro acquired drug resistance. The clinical relevance of topo II remains unclear, whereas a relationship between pgp levels and treatment results has been shown in acute myelogenous leukaemia (AML). We have investigated the relationships between the levels of topo II and pgp, and in vitro sensitivity to etoposide in mononuclear blood cells from 24 patients with AML, 16 with chronic lymphocytic leukaemia (CLL) and five healthy blood donors. Following incubation with etoposide, AML cells showed more DNA damage, determined by a DNA unwinding technique, than CLL cells (P = 0.001), whereas there was no difference in cellular etoposide accumulation. Pgp and topo IIbeta levels, determined by Western blot, showed a pronounced variation between patients, but no correlation with induced DNA damage, whereas topo IIalpha protein was undetectable. In the AML group, topo IIbeta expression correlated with pgp expression (rho = 0.7, P = 0.001, n = 24). The topo IIbeta expression was 147.4(+/-74.6)% in the pgp+ AML cells (n = 10), compared to 33.4(+/-27.8)% in pgp- AML cells (n = 14) (P = 0.0001). Our results show a previously unknown coexpression of topo IIbeta and pgp in AML, thereby suggesting that topo IIbeta is a potentially interesting resistance factor in AML. SN - 0007-1048 UR - https://www.unboundmedicine.com/medline/citation/10233413/Etoposide_induced_DNA_strand_breaks_in_relation_to_p_glycoprotein_and_topoisomerase_II_protein_expression_in_leukaemic_cells_from_patients_with_AML_and_CLL_ DB - PRIME DP - Unbound Medicine ER -