Therapy-induced drug resistance in a human leukemia line (LALW-2). A clinically relevant model.
A human leukemic T-cell line, LALW-2, established by xenografting in nude mice, has been maintained through 14 serial passages. The cells display consistent morphologic features, immunophenotype, and karyotypic aberrations (including an 11;14 translocation) and exhibit rearrangement of the T-cell receptor beta-chain gene. The growth rate of LALW-2 xenografts was differentially affected by drugs administered to host mice, the cells being resistant to cytotoxic agents (particularly methotrexate and doxorubicin) used in treatment of the donor patient. In short-term in vitro culture, LALW-2 cells exhibited extreme resistance to methotrexate and were also resistant to vincristine, vinblastine, dactinomycin, and doxorubicin. The findings differ from those obtained with laboratory-derived methotrexate or multidrug-resistant cell lines. The response of LALW-2 cells, in both the nude mouse model and in vitro, is consistent with acquisition of drug-resistance as a result of clinical treatment.
White
L
L
Children's Leukaemia and Cancer Research Unit, Prince of Wales Children's Hospital, Sydney, NSW, Australia.
Haber
M
M
Brian
M J
MJ
Norris
M D
MD
Trickett
A
A
Sosula
L
L
Tiley
C
C
Stewart
B W
BW
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007621:Karyotyping; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents