Inactivation of deoxycytidine kinase and overexpression of P-glycoprotein in AraC and daunorubicin double resistant leukemic cell lines

被引：17

作者：

Veuger, MJ ^{[1
]}

Honders, MW ^{[1
]}

Spoelder, HE ^{[1
]}

Willemze, R ^{[1
]}

Barte, RMY ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Hematol, Lab Expt Hematol, NL-2333 ZA Leiden, Netherlands

来源：

LEUKEMIA RESEARCH | 2003年 / 27卷 / 05期

关键词：

acute myeloid leukemia; cytarabine (AraC); daunorubicin; double resistance; deoxycytidine kinase; P-glycoprotein;

D O I：

10.1016/S0145-2126(02)00224-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

AraC resistance in vitro is explained by inactivation of dCK, while resistance to DNR is described by overexpression of multidrug efflux pumps like Pgp or MRP. Thusfar, no correlation between resistance mechanisms in vitro and in patients with AML has been documented. We generated AraC and DNR double resistant cell lines to investigate resistance mechanisms of both agents. In these cell lines involvement of dCK was extensively investigated and Pgp expression and activity was determined. Our data implicate that similar resistance mechanisms like inactivation of dCK coincided by alternatively spliced dCK forms and overexpression of Pgp are induced in single-as well as in double resistant leukemic cell lines. (C) 2003 Published by Elsevier Science Ltd.

引用

页码：445 / 453

页数：9

共 47 条

[31] Expression of breast cancer resistance protein in blast cells from patients with acute leukemia
Ross, DD
Karp, JE
Chen, TT
Doyle, LA
[J]. BLOOD, 2000, 96 (01) : 365 - 368
[32] Rowe JM, 1998, LEUKEMIA, V12, pS16
[33] SCHEPER RJ, 1993, CANCER RES, V53, P1475
[34] Schiller GJ, 1998, LEUKEMIA, V12, pS20
[35] INCREASED EXPRESSION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN GENE IN RELAPSED ACUTE-LEUKEMIA
SCHNEIDER, E
COWAN, KH
BADER, H
TOOMEY, S
SCHWARTZ, GN
KARP, JE
BURKE, PJ
KAUFMANN, SH
[J]. BLOOD, 1995, 85 (01) : 186 - 193
[36] STEGMANN APA, 1995, LEUKEMIA, V9, P1032
[37] IN VITRO-INDUCED RESISTANCE TO THE DEOXYCYTIDINE ANALOGS CYTARABINE (ARAC) AND 5-AZA-2'-DEOXYCYTIDINE (DAC) IN A RAT MODEL FOR ACUTE MYELOID-LEUKEMIA IS MEDIATED BY MUTATIONS IN THE DEOXYCYTIDINE KINASE (DCK) GENE
STEGMANN, APA
HONDERS, MW
HAGEMEIJER, A
HOEBEE, B
WILLEMZE, R
LANDEGENT, JE
[J]. ANNALS OF HEMATOLOGY, 1995, 71 (01) : 41 - 47
[38] Takemura H, 2001, CANCER RES, V61, P172
[39] Urasaki Y, 1996, ANTICANCER RES, V16, P709
[40] VANHAPEREN VWTR, 1994, CANCER RES, V54, P4138

← 1 2 3 4 5 →