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Growth and differentiation of the human megakaryoblastic cell line (ELF-
153): a model for early stages of megakaryocytopoiesis
MA Mouthon, M Freund, M Titeux, A Katz, J Guichard, J Breton-Gorius and W Vainchenker
INSERM U362, Institut Gustave Roussy, Villejuif, France.
ELF-153 is a cell line that has been established from a patient with a
poorly differentiated acute myeloid leukemia associated with an acute
myelofibrosis. A majority of cells had a blast morphology with the
phenotype of a myeloid hematopoietic progenitor, ie, CD34+, CD33+, CD13+,
HLA-DR+, but CD38-, and the remaining cells (5% to 10%) expressed platelet
restricted proteins such as CD41, CD42, CD36, CD61, and von Willebrand
factor; some of them were polyploid (up to 32N) and exhibited demarcation
membranes and alpha granules. No erythroid or other lineage-specific
markers were detected. Proliferation of ELF-153 cells was highly stimulated
by interleukin-3 (IL-3) and granulocyte- macrophage colony-stimulating
factor and to a lesser extent by stem cell factor and IL-6. In contrast,
the cell line did not respond to erythropoietin, leukemia inhibitory
factor, IL-7, IL-11, granulocyte colony-stimulating factor, and basic
fibroblast growth factor. ELF-153 cells could be separated by flow
cytometry into three discrete cell populations (CD34+/CD61-, CD34+/CD61+,
and CD34-/CD61+) with different proliferative and endomitotic properties
corresponding to distinct stages of the mega karyocyte (MK)
differentiation. This MK differentiation, which involved a minority of
ELF-153, could be increased in the presence of 5-azacytidine and phorbol
ester, but could not be significantly modified by growth factors. By
contrast, cytochalasin B dramatically induced polyploidization without
differentiation. It is noteworthy that association of 5-azacytidine to
cytochalasin B dramatically induced the production of polyploid MK cells.
To understand the molecular mechanisms underlying this MK differentiation,
the expression of GATA-1 and GATA-2 was investigated in subpopulations of
ELF-153. A high level of GATA-1 and GATA-2 mRNA was only present in the
CD61+ cells. Therefore, these two transactivating factors may play an
important role in the MK differentiation of ELF-153. We conclude that
ELF-153 might be an important tool to investigate the mechanisms by which
transcription factors control differentiation of MK progenitors.
Volume 84,
Issue 4,
pp. 1085-1097,
08/15/1994
Copyright © 1994 by The American Society of Hematology
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