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 Previous Article | Table of Contents | Next Article 
Megakaryocyte growth and development factor ameliorates carboplatin-
induced thrombocytopenia in mice
TR Ulich, J del Castillo, S Yin, S Swift, D Padilla, G Senaldi, L Bennett, J Shutter, J Bogenberger and D Sun
Amgen Inc., Thousand Oaks, CA 91320, USA.
Megakaryocyte growth and development factor (MGDF) administered
intraperitoneally (IP) to mice causes a dose-dependent thrombocytosis
accompanied by a decrease in mean platelet volume. MGDF increases the
number of megakaryocytes in the bone marrow and spleen. MGDF does not
affect the circulating number of leukocytes. Carboplatin, a
chemotherapeutic agent that causes thrombocytopenia in humans, administered
to mice as a single IP injection at a nonlethal dose causes a significant,
but reversible thrombocytopenia. The carboplatin- induced thrombocytopenia
is accompanied by an increase in circulating endogenous MGDF that precedes
the return of circulating platelets to a normal level. MGDF mRNA is
constitutively present in the liver. After carboplatin treatment, hepatic
MGDF mRNA does not increase in concordance with circulating MGDF.
Circulating soluble MGDF receptor levels (c-mpl) do not change
significantly during the course of carboplatin-induced thrombocytopenia.
MGDF injected IP once daily beginning 1 day after injection of carboplatin
reverses carboplatin- induced thrombocytopenia in a dose-dependent fashion.
The normalization of circulating platelet numbers in carboplatin plus
MGDF-treated mice is accompanied by a normalization of megakaryocyte
numbers in the bone marrow. In conclusion, MGDF, by increasing the number
of marrow megakaryocytes and circulating platelets is an effective therapy
for carboplatin-induced thrombocytopenia in mice.
Volume 86,
Issue 3,
pp. 971-976,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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