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Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces
lineage-specific growth and differentiation of megakaryocytes in mice
XQ Yan, D Lacey, F Fletcher, C Hartley, P McElroy, Y Sun, M Xia, S Mu, C Saris and D Hill
Department of Developmental Hematology, Amgen Inc, Thousand Oaks, CA
91320-1789, USA.
Megakaryocyte growth and development factor (MGDF) has recently been
identified as a ligand for the c-mpl receptor. Using retroviral- mediated
gene transfer, MGDF has been overexpressed in mice to evaluate the
systematic effects due to chronic exposure to this growth factor. MGDF
overexpressing mice had more rapid platelet recovery than control mice
after transplantation. Following this recovery, the platelet levels
continued increasing to fourfold to eightfold above normal baseline levels
and remained elevated (five-fold above control mice) in these animals,
which are alive and well at more than 4 months posttransplantation.
Increased megakaryocyte numbers were detected in a number of organs in
these mice including bone marrow, spleen, liver, and lymph nodes. Prolonged
overexpression of MGDF led to decreased marrow hematopoiesis, especially
erythropoiesis, with a shift to extramedullary hematopoiesis in the spleen
and liver. All the MGDF overexpressing mice analyzed to date developed
myelofibrosis and osteosclerosis, possibly induced by megakaryocyte and
platelet produced cytokines. No significant effect on other hematopoietic
lineages was seen in the MGDF overexpressing mice, showing that the
stimulatory effect of MGDF in vivo is restricted to the megakaryocyte
lineage.
Volume 86,
Issue 11,
pp. 4025-4033,
12/01/1995
Copyright © 1995 by The American Society of Hematology
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