The goal of this project is to increase our understanding of the terminal steps in megakaryocyte development. We will isolate subpopulations of megakaryocytes and subject them to electron microscopic, cytochemical and functional analysis. Megakaryocyte ploidy values will be correlated with the development of cellular organelles. The influence of thrombopoetin, erythropoietin and megakaryocyte colony stimulating activity on megakaryocyte organelle development will be assessed. Megakaryocyte organelle maturity and nuclear differentiation will be simultaneously assessed. Ultrastructural abnormalities of megakaryocytes obtained from patients with congenital and acquired disorders affecting platelets will be examined. The study of congenital and acquired qualitative platelet disorders will allow us to translate abnormalities in megakaryocyte development into resultant functional and ultrastructural defects in platelets.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031710-03
Application #
3342933
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Roth, B J; Sledge Jr, G W; Straneva, J E et al. (1988) Analysis of phorbol ester stimulated human megakaryocyte development. Blood 72:202-7
Hoffman, R; Lu, L; Jansen, J et al. (1988) Influence of T lymphocytes on hematopoiesis in a patient with T cell hypoplasia. Am J Hematol 27:118-24
Straneva, J E; Yang, H H; Hui, S L et al. (1987) Effects of megakaryocyte colony-stimulating factor on terminal cytoplasmic maturation of human megakaryocytes. Exp Hematol 15:657-63
Sledge Jr, G W; Glant, M; Jansen, J et al. (1986) Establishment in long term culture of megakaryocytic leukemia cells (EST-IU) from the marrow of a patient with leukemia and a mediastinal germ cell neoplasm. Cancer Res 46:2155-9
Straneva, J E; Goheen, M P; Hui, S L et al. (1986) Terminal cytoplasmic maturation of human megakaryocytes in vitro. Exp Hematol 14:919-29
Hoffman, R; Zaknoen, S; Yang, H H et al. (1985) An antibody cytotoxic to megakaryocyte progenitor cells in a patient with immune thrombocytopenic purpura. N Engl J Med 312:1170-4