Pegylated recombinant human megakaryocyte growth and development factor suppresses the development of megakaryoblastic leukemia in mice.
We examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on the development of L-8057, a murine megakaryoblastic leukemia that expresses the thrombopoietin receptor c-Mpl, in mice. PEG-rHuMGDF administration prolonged survival of L-8057 leukemic mice, in which L-8057 cell growth in the spleen was decreased. L-8057 cells harvested from PEG-rHuMGDF-treated leukemic mice had decreased ability to generate leukemic colonies in vitro as well as to induce leukemia in vivo. PEG-rHuMGDF administration also resulted in prolonged survival of mice transplanted with a c-Mpl-expressing erythroleukemia, but had no effect on survival of mice transplanted with a myeloblastic leukemia that does not possess c-Mpl. Thus, PEG-rHuMGDF suppresses the development of c-Mpl-expressing leukemia in vivo in mice.
Shibuya
Kazunori
K
Pharmaceutical Development Laboratories, Kirin Brewery Company Ltd., 3 Miyahara-cho, Takasaki, Gunma 370-1295, Japan.
Kuwaki
Tomoaki
T
Akahori
Hiromichi
H
Kato
Takashi
T
Miyazaki
Hiroshi
H
D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000188:drug therapy* / Q000517:prevention & control; D008099:Liver; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D015513:Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018121:Receptors, Cytokine / Q000032:analysis / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen; D015996:Survival Rate; D013926:Thrombopoietin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
C481270:Mpl protein, mouse; D015513:Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin