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[Cancer Research 50, 6793-6799, November 1, 1990]
© 1990 American Association for Cancer Research

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Susceptibility of Multidrug-resistant Human Leukemia Cell Lines to Human Interleukin 2-activated Killer Cells

Astrid Kimmig, Volker Gekeler, Manfred Neumann, Gerd Frese, Rupert Handgretinger, Gabriella Kardos, Heyke Diddens and Dietrich Niethammer1

Department of Hematology and Oncology, Children's University Hospital [A. K., R. H., G. K., D. N.], and Physiological Chemistry [V. G., G. F., M. N.], University of Tuebingen, Tuebingen, and Medical Laser Center, Luebeck [H. D.], West Germany

Considering the possibility to overcome drug resistance by other treatment strategies than chemotherapy we investigated the susceptibility of three independently selected multidrug-resistant sublines of the T-lymphoblastoid leukemic cell line CCRF-CEM to lymphokine-activated killer (LAK) cells. We found that two of the multidrug-resistant sublines were significantly less susceptible targets to LAK cells. A third one, however, was as susceptible as the parental CCRF-CEM cell line. Moreover, a multidrug-resistant subline that reverted to an almost drug-sensitive phenotype was observed to be also revertant for resistance against LAK cells. We found an inverse relationship between the expression of the mdr1 gene (P-glycoprotein) and the susceptibility of LAK cells. Verapamil, a calcium channel blocker, while increasing the drug sensitivity of a multidrug-resistant subline, did not induce a reversal of the suppression of LAK susceptibility. The possibility of enhanced resistance to LAK cells of multidrug-resistant cells should be taken into account when one is looking for therapy strategies to overcome multidrug resistance.

1 To whom requests for reprints should be addressed, at Children's University Hospital, Ruemelinstrasse 21-23, D-7400 Tuebingen 1, West Germany.

Received 10/17/89. Accepted 8/ 3/90.




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Cancer Research Clinical Cancer Research
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Copyright © 1990 by the American Association for Cancer Research.