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The relationship between multi-drug resistance and resistance to natural-killer-cell and lymphokine-activated killer-cell lysis in human leukemic cell lines

✍ Scribed by Robin S. Treichel; Sarah Olken


Publisher
John Wiley and Sons
Year
1992
Tongue
French
Weight
627 KB
Volume
50
Category
Article
ISSN
0020-7136

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✦ Synopsis


Abstract

Results concerning a possible link between susceptibility to natural‐cell‐mediated immune cytolysis and the multi‐drug resistance (MDR) phenotype are conflicting. We evaluated in human acute lymphocytic leukemia the relationship between acquired drug resistance and susceptibility to cytolysis mediated by endogenous, interferon‐activated, and interleukin‐2‐ activated natural cytotoxic celts. Eight human leukemia drug‐ resistant/sensitive cell line pairs were evaluated; drug‐resistant sub‐lines included those selected for primary resistance to adriamycin, etoposide, teniposide, vincristine, and vinblastine. A majority of P‐glycoprotein‐positive MDR sub‐lines displayed slight but statistically significant resistance to endogenous and/or interferon‐activated natural‐killer(NK)‐cell‐mediated lysis, as compared with the drug‐sensitive parental type. P‐glycoprotein‐ negative sub‐lines displayed variable NK susceptibility; within this group, the variants selected for primary etoposide resistance were more susceptible to NK cytolysis than parental cells. Results of cold‐target‐inhibition experiments suggest that altered NK susceptibility does not arise solely from modulation of NK target recognition and adherence structures. IL2‐activated killer (LAK) cells lysed both drug‐sensitive and drug‐resistant lines. Two MDR lines selected for primary etoposide resistance displayed enhanced LAK susceptibility. In contrast, the 2 variants selected for resistance to adriamycin exhibited partial resistance to LAK‐mediated killing, which could be overcome at high effector‐to‐target ratios. Our results support the development of interleukin‐2/LAK immunotherapy for the treatment of leukemias with acquired drug resistance.


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