Therapeutic potential of recombinant granulocyte-macrophage colony-
stimulating factor and interleukin-3 in murine B-cell leukemia
I Fabian, Y Kletter and S Slavin
Department of Histology and Cell Biology, Sackler Faculty of Medicine, Tel
Aviv, Israel.
The antileukemic activity of murine recombinant granulocyte-macrophage
colony-stimulating factor (rGM-CSF) and a combination of rGM-CSF and
recombinant interleukin-3 (rIL-3) was examined by using a murine model of
spontaneous B-cell leukemia (BCL1) in BALB/c mice. All untreated mice
inoculated with 2 x 10(2) BCL1 cells developed leukemia within 4 weeks,
with extreme lymphocytosis and a massive increase in both spleen weight and
cell number while the number of myeloid progenitors (CFU-C) per spleen was
decreased. In contrast, rGM-CSF-or rGM-CSF- and rIL-3- treated recipients
did not show any evidence of leukemia or splenomegaly at 4 weeks and showed
a significant increase in CFU-C per spleen. Hematologic parameters in the
peripheral blood of untreated mice showed anemia and thrombocytopenia.
Significant elevations in these parameters were recorded in mice treated
with either protocol of CSF. Treatment of recipient mice with either
rGM-CSF or rGM-CSF and rIL- 3 prolonged their median survival from 6 weeks
in untreated controls (range, 5 to 9 weeks) up to the time they were killed
at 105 days. Adoptive transfer of spleen cells obtained from mice treated
with rGM- CSF, mice treated with a combination of rGM-CSF and rIL-3, and
untreated controls, into normal secondary recipients indicated improved
survival in recipients inoculated with rGM-CSF. These data indicate that
CSFs may inhibit in vivo expansion of leukemic cells of lymphoid origin.
Volume 72,
Issue 3,
pp. 913-918,
09/01/1988
Copyright © 1988 by The American Society of Hematology
