Interferon protects normal human granulocyte/macrophage colony-forming cells from Ara-C cytotoxicity.
Interferons (IFN) have clinical efficacy in certain hematologic malignancies. Combining IFN with conventional cytotoxic agents has been proposed as a means of improving therapy for diseases such as chronic myelogenous leukemia (CML). In this study, we examined the effect of recombinant interferons alone and in combination with Ara-C on normal and leukemic human hematopoietic progenitor cells (CFU-GM) in vitro. Mononuclear cells from normal bone marrow, peripheral blood of patients with CML, or the acute nonlymphocytic leukemia cell line HL-60 were incubated with alpha-, beta-, or gamma-IFN (0-1,000 units/ml) followed by the addition of Ara-C. The survival of normal CFU-GM was significantly increased if cells were treated with IFN 1 h before 3 h of Ara-C exposure. Similar IFN pretreatment of CML and HL-60 progenitors failed to protect leukemic CFU-GM from Ara-C-induced toxicity. This selective protection of normal CFU-GM may have clinical application.
Richman
C M
CM
Department of Medicine, Thomas Hazen Thorne Bone Marrow Transplant Center, Rush Medical College, Chicago, Illinois.
Slapak
C A
CA
Toh
B
B
D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007372:Interferons / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003561:Cytarabine; D007372:Interferons