Leukemia Research
Volume 27, Issue 5 , Pages 445-453, May 2003

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

Laboratory of Experimental Hematology, C2-R, Leiden University Medical Center, Department of Hematology, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands

Received 18 March 2002; accepted 28 September 2002.

Abstract 

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.

Keywords:  Acute myeloid leukemia, Cytarabine (AraC), Daunorubicin, Double resistance, Deoxycytidine kinase, P-glycoprotein

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PII: S0145-2126(02)00224-2

doi:10.1016/S0145-2126(02)00224-2

Leukemia Research
Volume 27, Issue 5 , Pages 445-453, May 2003

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