Induction of dependence on hematopoietic proteins for viability and
receptor upregulation in differentiating myeloid leukemic cells
J Lotem and L Sachs
Department of Genetics, Weizmann Institute of Science, Rehovot, Israel.
There are different types of myeloid leukemic cells that can be induced to
differentiate to mature granulocytes or macrophages by different
hematopoietic regulatory proteins. One type of leukemic clone can be
induced to differentiate by recombinant macrophage and granulocyte
differentiation-inducing protein-type 2 (MGI-2), which we have shown is
Interleukin-6 (IL-6), and another type of leukemic clone can be
differentiated by recombinant granulocyte-macrophage colony-stimulating
factor (GM-CSF) or IL-3. There was no subpopulation of growth factor-
responsive or differentiation-defective cells before induction of
differentiation in either type of clone. In both clones, induction of
differentiation-induced requirement for a hematopoietic protein for cell
viability. Viability of the cells was maintained by IL-6, IL-3, or
macrophage colony-stimulating factor (M-CSF) but not by GM-CSF in the cells
differentiated by IL-6, and by GM-CSF or IL-3 but not by IL-6 or M-CSF in
the cells differentiated by GM-CSF or IL-3. The viable cells with a
differentiated phenotype continued to multiply. In undifferentiated
leukemic cells with no or few surface receptors for some of these proteins,
there was an upregulation of the number of receptors during differentiation
for the proteins to which the cells responded. But there were also
differentiating leukemic cells with an upregulation of GM-CSF receptors
although GM-CSF could not maintain the viability of the differentiating
cells. The results indicate that induction of hormone responsiveness and
upregulation of the hormone receptors can both occur in differentiating
leukemic cells, and that the regulation of these two events can be
separated.
Volume 74,
Issue 2,
pp. 579-585,
08/01/1989
Copyright © 1989 by The American Society of Hematology
