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Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte
hyperplasia in mice
TR Ulich, J del Castillo, G Senaldi, O Kinstler, S Yin, S Kaufman, J Tarpley, E Choi, T Kirley, P Hunt and WP Sheridan
Amgen Inc, Thousand Oaks, CA 91320, USA.
PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent
increase in megakaryocytes and platelets. At the same time that platelet
numbers are increased, the mean platelet volume (MPV) and platelet
distribution width (PDW) can be either decreased, normal, or increased
depending on the dose and time after administration. Thus, PEG-rHuMGDF at a
low dose causes decreases in MPV and PDW, MGDF at an intermediate dose
causes an initial increase followed by a decrease in MPV and PDW, and
PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a
gradual normalization of these platelet indices. In addition to the
expected thrombocytosis after 7 to 10 days of daily injection of high doses
of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers
and hemoglobin is noted accompanied in the bone marrow by megakaryocytic
hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and
deposition of a fine network of reticulin fibers. Splenomegaly, an increase
in splenic megakaryocytes, and extramedullary hematopoiesis accompany the
hematologic changes in the peripheral blood and marrow to complete a
spectrum of pathologic features similar to those reported in patients with
myelofibrosis and megakaryocyte hyperplasia. However, all the
PEG-rHuMGDF-initiated hematopathology including the increase in marrow
reticulin is completely and rapidly reversible upon the cessation of
administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation
of megakaryocytes does not cause irreversible tissue injury. Furthermore,
PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at
a low-dose that does not cause the hematopathology associated with
myelofibrosis.
Volume 87,
Issue 12,
pp. 5006-5015,
06/15/1996
Copyright © 1996 by The American Society of Hematology
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