Faculty Collaboration Database

Synergistic antiproliferative effect of interferon alpha and azidothymidine in chronic myelogenous leukemia. Leukemia 1991 Feb;5(2):101-7

Date

02/01/1991

Pubmed ID

2020193

Scopus ID

2-s2.0-0026049469 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

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.

Author List

Estrov Z, Talpaz M, Chou TC, Kurzrock R, Blake M, Gutterman JU

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Dose-Response Relationship, Drug
Drug Synergism
Erythroid Precursor Cells
Female
Hematopoiesis
Hematopoietic Stem Cells
Humans
In Vitro Techniques
Interferon Type I
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Zidovudine