Alpha-interferon broadens the difference between surviving fractions of normal and leukemic progenitor cells in vitro by heat: its application to marrow purging.
Alpha-interferon (IFN) may inhibit the proliferation of human leukemic progenitor cells (L-CFU) in vitro and enhance the anti-tumor effects by heat. In this study, the combined effects of IFN and hyperthermia on the growth of L-CFU and human granulocyte-macrophage progenitors (CFU-GM) were examined to determine if this combination resulted in a greater selective killing of L-CFU than that obtained by heat treatment alone. The survival of normal CFU-GM without IFN decreased at elevated temperatures (42-44 degrees C). However, IFN added during heating (42 and 43 degrees C) appeared significantly to protect against the hyperthermic killing of CFU-GM in vitro leaving over 50% of CFU-GM surviving. The optimal dose to protect CFU-GM in vitro dropped to a rather low dose (100 U/ml). On the other hand, the addition of IFN to leukemic cell suspensions enhanced the hyperthermic killing of myeloid leukemic cell lines (HEL and KG-1) as well as a T lymphoblastic cell line (CEM) in a dose-related manner. In addition, similar results were observed in the study of L-CFU from patients with acute myelogenous leukemia. These results suggest that IFN can be used to broaden the difference between surviving fractions of CFU-GM and L-CFU by heat. Thus, this combination could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous remission marrow graft before autologous bone marrow transplantation.
Moriyama
Y
Y
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
Goto
T
T
Nikkuni
K
K
Aoki
A
A
Furukawa
T
T
Narita
M
M
Koyama
S
S
Kishi
K
K
Takahashi
M
M
Shibata
A
A
D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D005069:Evaluation Studies as Topic; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha; D007938:Leukemia / Q000473:pathology / Q000601:surgery*; D014411:Neoplastic Stem Cells / Q000473:pathology
D016898:Interferon-alpha