Megakaryocyte growth and development factor. Analyses of in vitro effects on human megakaryopoiesis and endogenous serum levels during chemotherapy-induced thrombocytopenia.

Abstract

The present study shows that recombinant human megakaryocyte growth and development factor (r-HuMGDF) behaves both as a megakaryocyte colony stimulating factor and as a differentiation factor in human progenitor cell cultures. Megakaryocyte colony formation induced with rHuMGDF is synergistically affected by stem cell factor but not by interleukin 3. Megakaryocytes stimulated with rHuMGDF demonstrate progressive cytoplasmic and nuclear maturation. Measurable levels of megakaryocyte growth and development factor in serum from patients undergoing myeloablative therapy and transplantation are shown to be elaborated in response to thrombocytopenic stress. These data support the concept that megakaryocyte growth and development factor is a physiologically regulated cytokine that is capable of supporting several aspects of megakaryopoiesis. (J. Clin. Invest. 1995Invest. . 95:2973Invest. -2978

Serum thrombopoietin levels in patients correlate inversely with platelet counts during chemotherapy-induced thrombocytopenia

“…20 Because serum TPO levels are very low in humans and difficult to quantify, levels have generally been estimated indirectly by the bioassay of megakaryocyte stimulating activity 16 or by the proliferation assay of TPO-responsive cell lines. 17,21 In these bioassays, non-specific stimulators or inhibitors in the blood samples may affect the estimation. Recently, Emmons et al 19 reported a receptor captured enzyme immunoassay for TPO in humans.…”

“…16 Also in human studies, TPO levels changed reciprocally to platelet counts in patients with cyclic thrombocytopenia or undergoing bone marrow transplantation after myeloablative therapy. [21][22][23][24] On the other hand, it was described that TPO levels were high when thrombocytopenia was due to megakaryocyte deficiency, and low when due to increased platelet destruction, 19 and that serum megakaryocyte colony-stimulating activity levels appeared to be inversely related to marrow megakaryocyte numbers. 25 In the present study, we could clearly demonstrate using a sensitive ELISA that human TPO levels also changed inversely with the number of platelets after myelosuppressive chemotherapy.…”

Neutralization of Biological Activity and Inhibition of Receptor Binding by Antibodies Against Human Thrombopoietin

“…TPO stimulates the growth of committed megakaryocyte progenitors, the progressive maturation of megakaryocytes, and proplatelet formation [2][3][4][5][6][7][8]. In addition to its stimulating effect on megakaryocytopoiesis, TPO has also been reported to affect committed erythroid progenitors [9], hematopoietic progenitor cells [10], and leukemia cells [11].…”

Effects of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor on Thrombocytopenia Induced by a New Myelosuppressive Chemotherapy Regimen in Mice

“…TPO supports the formation of megakaryocyte colonies from murine bone marrow cells and human CD34 + cells in semisolid cultures [19,[25][26][27][28][29][30][31]. TPO also serves as a potent megakaryocyte maturation factor, because megakaryocytes generated in liquid culture containing TPO exhibit a marked increase in ploidy classes and well-developed demarcation membranes in their cytoplasm [26,27,29,31].…”