Hematopoietins in combination with 1-beta-D-arabinofuranosylcytosine: a possible strategy for improved treatment of myeloid disorders.
Inhibitors of DNA synthesis, such as 1-beta-D-arabinofuranosylcytosine, have been proven useful in the management of acute myelogenous leukemia. Despite significant improvement of response rates, long-term disease-free survival can be presently achieved only in a small percentage of patients. As S-phase--specific drugs, such as the inhibitors of DNA synthesis, only reach the cycling part of their target populations, dormant cells are left mainly unaffected. Their survival, however, is largely responsible for later disease relapse. This paper reports experiments that show that cell kinetic manipulations by hematopoietic growth factors may help to overcome the problem of cytokinetic and pharmacologic resistance. Hematopoietic growth factors synergize with inhibitors of DNA synthesis given at low doses to induce a more mature phenotype or to enhance leukemia cell kill when combined with high doses of DNA inhibitors. In addition, we present data to unravel several aspects of the molecular mechanism underlying this synergism.
Brach
M A
MA
Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
Mertelsmann
R H
RH
Herrmann
F
F
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003561:Cytarabine / Q000378:metabolism / Q000627:therapeutic use; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000628:therapy*; D016196:S Phase / Q000187:drug effects*
D000970:Antineoplastic Agents; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor