In vivo development of cytosine arabinoside resistance in the BN acute myelocytic leukemia

Semin Oncol. 1987 Jun;14(2 Suppl 1):202-6.

Abstract

The in vivo development of an ara-C-resistant leukemic cell line is reported in a rat leukemia model (BNML) that is generally accepted as a relevant model for human acute myelocytic leukemia. It took 32 continuous leukemia transplant generations, performed over 20 months, and a total dose of 28.5 g ara-C/kg to induce complete resistance. Preliminary data indicate that the development of ara-C resistance is related with decreased intracellular levels of deoxycytidine kinase. Deoxycytidine deaminase levels were not increased. Thus this enzyme does not seem to be involved with induction of resistance. This preclinical rat model for human AML provides a solid basis for studies in depth on the mechanism(s) and possible prevention and effective treatment of resistance to ara-C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytarabine / therapeutic use*
  • Cytidine Deaminase
  • Deoxycytidine Kinase / metabolism
  • Drug Resistance*
  • Leukemia, Experimental / drug therapy*
  • Leukemia, Myeloid, Acute / drug therapy
  • Nucleoside Deaminases / metabolism
  • Rats

Substances

  • Cytarabine
  • Deoxycytidine Kinase
  • Nucleoside Deaminases
  • Cytidine Deaminase
  • deoxycytidine deaminase