Ether lipids are effective cytotoxic drugs against multidrug-resistant acute leukemia cells and can act by the induction of apoptosis.
We studied the cytotoxic effects of two ether lipids, a relatively new class of anticancer drugs, on multidrug-resistant (MDR1) leukemia cells of patients with acute leukemias who had failed induction treatment. The cytotoxicity of ether lipids was determined by the elimination of clonogenic leukemia cells from leukemic cultures or, in case of failure to generate leukemic cultures, by the inhibition of 3[H]thymidine incorporation in leukemic blasts. At dose levels of 50 microg/ml, a plasma level that can be achieved after oral intake, the MDR1-positive blasts were killed, both of patients with drug-resistant acute myeloid leukemia (AML) and of patients with drug-resistant acute lymphoblastic leukemia (ALL). The leukemic blasts were killed by the induction of apoptosis. These data suggest that ether lipids may be effective antileukemic drugs and that their cytotoxic function is not affected by MDR1.
Verdonck
L F
LF
Department of Haematology, University Hospital, Utrecht, The Netherlands. J.vd.Velde@digd.azu.nl
van Heugten
H G
HG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D014410:Tumor Stem Cell Assay
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C026659:edelfosine; C039128:miltefosine