In vivo control of differentiation of myeloid leukemic cells by recombinant
granulocyte-macrophage colony-stimulating factor and interleukin 3
J Lotem and L Sachs
Department of Genetics, Weizmann Institute of Science, Rehovot, Israel.
The normal myeloid hematopoietic regulatory proteins include one class of
proteins that induces viability and multiplication of normal myeloid
precursor cells to form colonies (colony-stimulating factors [CSF] and
interleukin 3 [IL-3], macrophage and granulocyte inducing proteins, type 7
[MGI-1]) and another class (called MGI-2) that induces differentiation of
normal myeloid precursors without inducing cell multiplication. Different
clones of myeloid leukemic cells can differ in their response to these
regulatory proteins. One type of leukemic clone can be differentiated in
vitro to mature cells by incubating with the growth-inducing proteins
granulocyte-macrophage (GM) CSF or IL-3, and another type of clone can be
differentiated in vitro to mature cells by the differentiation-inducing
protein MGI-2. We have now studied the ability of different myeloid
regulatory proteins to induce the in vivo differentiation of these
different types of mouse myeloid leukemic clones in normal and
cyclophosphamide-treated mice. The results show that in both types of mice
(a) the in vitro GM-CSF- and IL- 3-sensitive leukemic cells were induced to
differentiate to mature cells in vivo in mice injected with pure
recombinant GM-CSF and IL-3 but not with G-CSF, M-CSF, or MGI-2; (b) the in
vitro MGI-2-sensitive leukemic cells differentiated in vivo by injection of
MGI-2 and also, presumably indirectly, by GM-CSF and IL-3 but not by M-CSF
or G-CSF; (c) in vivo induced differentiation of the leukemic cells was
associated with a 20- to 60-fold decrease in the number of blast cells; and
(d) all the injected myeloid regulatory proteins stimulated the normal
myelopoietic system. Different normal myeloid regulatory proteins can thus
induce in vivo terminal differentiation of leukemic cells, and it is
suggested that these proteins can have a therapeutic potential for myeloid
leukemia in addition to their therapeutic potential in stimulating normal
hematopoiesis.
Volume 71,
Issue 2,
pp. 375-382,
02/01/1988
Copyright © 1988 by The American Society of Hematology
