Are MTT assays the right tool to analyze drug resistance caused by ABC-transporters in patient samples?
Drug resistance can be caused by ATP-binding-cassette (ABC)-transporters which function as outward pumps for chemotherapeutic drugs. The aim of the present study was to analyze the association between eight ABC-transporters (BCRP, MDR1, SMRP, MRP1, MRP2, MRP3, MRP4, and MRP5) and in vitro drug resistance. Leukemic cells from 52 children with previously untreated acute leukemia (ALL: n=37; AML: n=15) were analysed. The expression of the ABC-transporters was measured by TaqMan real-time PCR. In vitro drug resistance to cytarabine, vincristine, tioguanine, daunorubicin, etoposide, dexamethasone, and prednisone was analysed with methyl-thiazol-tetrazolium (MTT) assays.MDR1 was weakly associated with resistance to vincristine (p<0.05) in AML samples. No other correlation between an ABC-transporter and a higher in vitro drug resistance was found. In vitro drug resistance was not associated with the simultaneous expression of a larger number of ABC-transporters.MTT assays are a widely used and validated method to analyse in vitro drug resistance but they may not be a useful tool to detect resistance which is caused by drug efflux in patient samples. If that is the case, MTT assays and the expression of ABC-transporters could provide complementary information on the drug resistance profile of patients with acute leukemia.
Steinbach
Daniel
D
University of Jena, Children's Hospital, Jena, Germany. Daniel@Steinba.ch
Friedrich
Jana
J
Dawczynski
Kristin
K
Furchtbar
Silke
S
Gruhn
Bernd
B
Wittig
Susann
S
Zintl
Felix
F
Sauerbrey
Axel
A
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D007928:Lethal Dose 50; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents