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Expression of bcr-abl abrogates factor-dependent growth of human
hematopoietic M07E cells by an autocrine mechanism
C Sirard, P Laneuville and JE Dick
Department of Genetics, Hospital for Sick Children, Toronto, Ontario,
Canada.
The introduction of a retrovirus vector expressing p210bcr-abl (P210) into
the human factor-dependent cell line M07E resulted in the rapid outgrowth
of factor-independent cells. Early after infection, four factor-independent
clones were isolated and analyzed in greater detail along with mass
populations obtained from separate infections. High levels of P210 tyrosine
kinase activity were measured in the factor- independent cells. The mass
populations and three of the four clones remained responsive to exogenous
growth factors. Concentrated conditioned media isolated from the
factor-independent populations and from all clones contained biologically
active granulocyte-macrophage colony-stimulating factor (GM-CSF);
interleukin-3 (IL-3) was detected at low levels in the mass population and
in two of the clones. Neutralizing antibodies to IL-3, GM-CSF, and mast
cell growth factor inhibited proliferation of the factor responsive clones
by 60% to 90%. These results indicate that the growth autonomy of the
P210-expressing M07E cells was acquired via an autocrine mechanism. In
addition to factor-independent growth, P210-expressing M07E cells readily
acquired a more mature megakaryocytic phenotype compared with control M07E
cells. These data provide experimental evidence that expression of P210
tyrosine kinase in human hematopoietic cells induced growth factor
secretion resulting in a pleiotropic effect on growth factor dependence and
differentiation.
Volume 83,
Issue 6,
pp. 1575-1585,
03/15/1994
Copyright © 1994 by The American Society of Hematology
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