Synergistic antiproliferative effect of interferon alpha and azidothymidine in chronic myelogenous leukemia.
The possible synergistic interaction between azidothymidine (AZT) and interferon alpha (rIFN-alpha 2a) in the treatment of chronic myelogenous leukemia (CML) was studied in vitro using marrow or peripheral blood hematopoietic progenitors from 10 patients with CML in the mixed (CFU-GEMM) colony culture assay. Used singly, either agent inhibited erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) CML hematopoietic progenitor proliferation in a dose-dependent fashion, with the inhibitory effect being more pronounced on BFU-E than on CFU-GM colony-forming cells. The combination of both drugs in therapeutic concentrations exerted a significant synergistic inhibition on CML stem cells as assessed by the median-effect principle and isobologram equation analysis. A suboptimal dose of AZT (0.5 mumol/l) synergistically augmented the effect of rIFN-alpha 2a whereas an inactive dose of 10 U/ml rIFN-alpha 2a similarly enhanced the CML stem cell growth inhibition exerted by AZT. Our data indicate that AZT may augment the already established therapeutic benefits of IFN-alpha in CML.
Estrov
Z
Z
Department of Clinical Immunology and Biological Therapy, University of Texas MD Anderson Cancer Center, Houston 77030.
Talpaz
M
M
Chou
T C
TC
Kurzrock
R
R
Blake
M
M
Gutterman
J U
JU
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015215:Zidovudine / Q000494:pharmacology*
D007370:Interferon Type I; D015215:Zidovudine