Annals of Hematology

, Volume 69, Issue 1, pp S19–S24 | Cite as

Drug-induced changes in the expression of MDR-associated genes: Investigations on cultured cell lines and chemotherapeutically treated leukemias

  • V. Gekeler
  • J. Beck
  • A. Noller
  • A. Wilisch
  • G. Frese
  • M. Neumann
  • R. Handgretinger
  • G. Ehninger
  • H. Probst
  • D. Niethammer
First Workshop of CSG-CR


The induced expression of multiple drug resistance (MDR)-associated genes as a direct response of tumor cells to antineoplastic drugs could be an important factor influencing the success of cancer chemotherapy. We investigated the effects of such compounds on mdr1/P-glycoprotein (P-gp) gene expression and drug sensitivities in the T-lymphoblastoid human cell line CCRF-CEM and MDR sublines. Thereby, we observed that actinomycin D or adriamycin administered at sublethal concentrations induced increases of mdr1 mRNA levels and resistance within 72 h. Furthermore, on leukemia cell samples collected before and after chemotherapy we checked by a complementary DNA polymerase chain reaction (cDNA-PCR) approach for similar alterations in the relative expression levels of the MDR-associated genes (a) mdr1/P-gp (b) mrp (MDR related protein), and (c) the topoisomerase II isoformsα andΒ. We found a concomitant increase in mdr1 and mrp gene expression combined with a decreased expression of topoisomerase IIα in the course of the second relapse of an acute lymphoblastic leukemia (ALL). This points to the emergence of at least three different MDR mechanisms in this type of leukemia unresponsive to chemotherapy. A chronic myeloid leukemia (CML) in blast crisis, however, showed combined increases in mdr1 (about 20-fold) and mrp (about four fold) gene expression after intense but unsuccessful chemotherapy over a 6-month period. Our results indicate the occurrence of induced resistance in vitro and in vivo and suggest a contribution of the newly identified ATP-binding cassette (ABC) transporter MRP in MDR.


Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Adriamycin Actinomycin Blast Crisis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Cooperative Study Group — Cellular Resistance


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • V. Gekeler
    • 1
  • J. Beck
    • 2
  • A. Noller
    • 3
  • A. Wilisch
    • 3
  • G. Frese
  • M. Neumann
    • 3
  • R. Handgretinger
    • 2
  • G. Ehninger
    • 4
  • H. Probst
    • 3
  • D. Niethammer
    • 2
  1. 1.Abteilung FP3Byk Gulden GmbHKonstanzGermany
  2. 2.KinderklinikUniversität TübingenTübingenGermany
  3. 3.Physiologisch-Chemisches InstitutUniversität TübingenTübingenGermany
  4. 4.Medizinische KlinikTübingenGermany

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