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Effects of human stem cell factor (c-kit ligand) on proliferation of
myeloid leukemia cells: heterogeneity in response and synergy with other
hematopoietic growth factors
T Pietsch, U Kyas, U Steffens, E Yakisan, MR Hadam, WD Ludwig, K Zsebo and K Welte
Department of Pediatric Hematology and Oncology, Medical School Hannover,
Germany.
A novel hematopoietic growth factor, the stem cell factor (SCF), for
primitive hematopoietic progenitor cells has recently been purified and its
gene has been cloned. In this study we tested the mitogenic activity of
recombinant human SCF on myeloid leukemia cells as well as the expression
of its receptor. We have investigated the proliferation of 31 myeloid
leukemia cell lines as well as fresh myeloid leukemic blasts from 17
patients in a 72-hour 3H-thymidine uptake assay in the presence of various
concentrations of recombinant human (rh) SCF alone or in combination with
saturating concentrations of granulocyte- macrophage colony-stimulating
factor (GM-CSF), G-CSF, M-CSF, interleukin-3 (IL-3), or erythropoietin
(EPO). Only five of 31 lines, but fresh leukemic blasts from 12 of 17
patients with acute myeloid leukemia (AML), significantly responded to SCF.
The responding cell lines were of the acute promyelocytic, chronic myeloid,
megakaryoblastic, and erythroleukemia origin, the responding blast
preparations of all French-American-British subtypes. Synergistic
activities of SCF were found with G-CSF, GM-CSF, EPO, and IL-3. To
determine the SCF binding sites on leukemic cells, we used 125I-
radiolabeled SCF in Scatchard analysis and cross-linking studies. The
leukemic cell lines responding to SCF expressed from 2,300 up to 29,000
binding sites per cell. The SCF receptor expression was downregulated in
vitro by the presence of its ligand. Cross-linking studies demonstrated a
150-Kd SCF receptor on the surface of all responding myeloid leukemias.
This study suggests that SCF may be an important factor for the growth of
myeloid leukemia cells, either as a direct stimulus or as a synergistic
factor for other cytokines. Furthermore, using polymerase chain reaction
analysis of total RNA from the myeloid leukemia lines, we found expression
of SCF-mRNA in 17 of 30 lines, suggesting autocrine mechanisms in the
growth of a subgroup of leukemic cells by coexpression of SCF and its
receptor.
Volume 80,
Issue 5,
pp. 1199-1206,
09/01/1992
Copyright © 1992 by The American Society of Hematology

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