Multidrug-resistant acute leukemia cells are responsive to prolonged exposure of daunorubicin: Implications for liposome-encapsulated daunorubicin

• Published in: Leukemia research Vol. 22; no. 3; pp. 249 - 256
• Main Authors: Verdonck, Leo F., Lokhorst, Henk M., Roovers, Dick J., van Heugten, Hans G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.1998; Elsevier Science
• Subjects: acute leukemia; Adult; Antibiotics, Antineoplastic - administration & dosage; Antineoplastic agents; Biological and medical sciences; Daunorubicin - administration & dosage; Drug Resistance, Multiple; Female; General aspects; Humans; Leukemia, Myeloid, Acute - drug therapy; Leukemia-Lymphoma, Adult T-Cell - drug therapy; liposomal daunorubicin; Liposomes; Male; Medical sciences; Middle Aged; multidrug resistance; Pharmacology. Drug treatments; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; multidrug resistance; liposomal daunorubicin; acute leukemia; Antineoplastic agent; Human; Acute; Liposome; Cytotoxicity; Malignant hemopathy; In vitro; Antibiotic; Daunorubicin; Lymphoproliferative syndrome; Multiple resistance; Dosage form; Anthracyclins; Acute lymphocytic leukemia; Acute myelocytic leukemia
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/S0145-2126(97)00160-4

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.