Multidrug-resistant acute leukemia cells are responsive to prolonged exposure of daunorubicin: implications for liposome-encapsulated daunorubicin.
We examined the cytotoxic effects of free daunorubicin (DNR) and liposome-encapsulated DNR on multidrug-resistant (MDR1) leukemia cells of patients with acute leukemias who had failed primary induction treatment that included DNR. This was analyzed ex-vivo with DNR concentrations and exposure times that normally can be achieved in-vivo for both drugs with induction treatment. The leukemic blasts of patients both with drug-resistant AML and drug-resistant ALL were, ex-vivo, very sensitive to DNR concentrations and exposure times that can be achieved in-vivo by liposome-encapsulated DNR. However, under identical conditions, free DNR and liposome-encapsulated DNR had a similar cytotoxic profile, arguing against a unique mechanism of cytotoxicity by the liposomal constructure. These data suggest that liposome-encapsulated DNR may be preferable to free DNR for the treatment of acute leukemias.
Verdonck
L F
LF
Department of Haematology, University Hospital Utrecht, The Netherlands. j.vd.velde@digd.azu.nl
Lokhorst
H M
HM
Roovers
D J
DJ
van Heugten
H G
HG
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D003630:Daunorubicin / Q000008:administration & dosage*; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D003630:Daunorubicin