Therapy-induced drug resistance in a human leukemia line (LALW-2)

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Abstract
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 β‐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 aquisition of drug‐resistance as a result of clinical treatment.