In vivo control of differentiation of myeloid leukemic cells by
cyclosporine A and recombinant interleukin-1 alpha
J Lotem and L Sachs
Department of Genetics, Weizmann Institute of Science, Rehovot, Israel.
There are different types of hematopoietic regulatory proteins that
regulate the multiplication and differentiation of normal myeloid cells.
These different types include four growth-inducing proteins called
colony-stimulating factors (CSF), including interleukin-3 (IL- 3), or
macrophage and granulocyte inducers, type 1 (MGI-1); another type (called
MGI-2) that induces myeloid differentiation of normal myeloid cells without
inducing myeloid cell multiplication; and interleukin-1 (IL-1), which can
act on myeloid precursor cells. Different clones of myeloid leukemic cells
can differ in their ability to be induced to undergo terminal cell
differentiation by different hematopoietic regulatory proteins. We have now
studied the ability of cyclosporine A and recombinant IL-1 alpha to
regulate in vivo differentiation of different clones of myeloid leukemic
cells that are either susceptible or resistant to induction of
differentiation by IL-1 in vitro. The results show that (a) cyclosporine A,
like other immune- suppressing compounds such as cyclophosphamide,
inhibited in vivo differentiation of myeloid leukemic cells and
differentiation was restored by injecting recombinant GM-CSF; (b)
recombinant IL-1 alpha induced in vivo terminal differentiation of
IL-1-sensitive but not IL-1- resistant clones of myeloid leukemic cells;
(c) IL-1 alpha and GM-CSF synergistically induced differentiation in vivo
in a GM-CSF-responsive and IL-1-nonresponsive clone of leukemic cells; and
(d) IL-1 alpha induced in vivo the rapid production and release into serum
of the differentiation-inducing protein MGI-2 as well as the
growth-inducing proteins M-CSF and G-CSF.
Volume 72,
Issue 5,
pp. 1595-1601,
11/01/1988
Copyright © 1988 by The American Society of Hematology
