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
收藏
页码：445 / 453
页数：9
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