In vivo therapeutic effects of IFN-gamma on human myelogenous leukemia in a severe combined immunodeficiency mouse model.
BACKGROUND
Results of clinical trials of IFN-gamma on the treatment of various types of leukemia are not so promising, regardless of the antiproliferative activity against leukemic cells and expected immunomodulatory effects. In this study, we have re-evaluated the anti-leukemic effects of natural human IFN-gamma (nHuIFN-gamma) using an established human myelogenous leukemia model in SCID mice.


METHODS
SCID mice transplanted with human myelogenous leukemia cell line ML-2S received subcutaneously 5 x 10(4) IU/mouse of nHuIFN-gamma at 5 times/week for 5 weeks.


RESULTS
nHuIFN-gamma significantly prolonged the lifespan of SCID mice in leukemic crisis. Percentages of ML-2S cells in the peripheral blood were also significantly decreased by the IFN-gamma treatment. Histopathological examination revealed that IFN-gamma treatment suppressed the replacement of pancreatic cells by tumor cells and the formation of tumor masses in the intestine.


CONCLUSIONS
These results suggest that IFN-gamma is effective against human myeloid leukemia, especially extramedullary tumor mass-forming type in the peritoneal organs. Our results further suggest that studies employing SCID mice leukemia model would help in devising appropriate therapeutic strategies of IFN-gamma based on the specific characteristics of each leukemia subtype.
Arai
C
C
Nagano Laboratory, Hayashibara Biochemical Labs, Inc., Okayama, Japan. fujisaki@hayashibara.co.jp
Tsuzaki
Y
Y
Nagano
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007371:Interferon-gamma