Effect of mast cell growth factor (c-kit ligand) on clonogenic leukemic
precursor cells
HM Goselink, DE Williams, WE Fibbe, HW Wessels, GC Beverstock, R Willemze and JH Falkenburg
Department of Hematology, University Medical Center, Leiden, The
Netherlands.
Mast cell growth factor (MGF), the ligand for the c-kit receptor, has been
shown to be a hematopoietic growth factor that preferentially stimulates
the proliferation of immature hematopoietic progenitor cells (HPC). We
studied the effect of MGF on the in vitro growth of clonogenic leukemic
precursor cells in the presence or absence of interleukin-3 (IL-3),
granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or
erythropoietin (EPO). Leukemic blood and bone marrow cells from patients
with various types of acute myeloid leukemia (AML), chronic myeloid
leukemia (CML) in chronic phase, as well as bone marrow samples from
patients with myelodysplastic syndromes (MDS) were studied. MGF as a single
factor did not induce significant colony formation by clonogenic leukemic
precursor cells. In the presence of IL- 3 and/or GM-CSF, MGF weakly
stimulated the colony formation by clonogenic precursor cells from patients
with AML. In contrast, in the presence of IL-3 and/or GM-CSF, MGF strongly
induced both size and number of leukemic colonies from patients with CML in
chronic phase. Furthermore, in the presence of EPO, MGF strongly stimulated
erythroid colony formation by CML precursor cells. Cytogenetic analysis of
the colonies showed that all metaphases after 1 week of culture were
derived from the leukemic clone. In patients with MDS, MGF strongly
stimulated myeloid colony formation in the presence of IL-3 and/or GM- CSF
(up to fourfold), and erythroid colony formation in the presence of EPO (up
to eightfold). Not only the number, but also the size of the colonies
increased. In the presence of MGF, the percentage of normal metaphases
increased in three patients tested after 1 week of culture compared with
the initial suspension, suggesting that the normal HPC were preferentially
stimulated compared with the preleukemic precursor cells. In the absence of
exogenous EPO and in the presence of 10% human AB serum, MGF in the
presence of IL-3 and/or GM-CSF induced erythroid colony formation from
normal bone marrow and patients with MDS or CML, illustrating that MGF
greatly diminished the EPO requirement for erythroid differentiation. These
results indicate that MGF may be a candidate as a hematopoietic growth
factor to stimulate normal hematopoiesis in patients with acute myeloid
leukemia, or with myelodysplastic syndromes.
Volume 80,
Issue 3,
pp. 750-757,
08/01/1992
Copyright © 1992 by The American Society of Hematology
