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Transforming growth factor beta selectively inhibits normal and leukemic
human bone marrow cell growth in vitro
GK Sing, JR Keller, LR Ellingsworth and FW Ruscetti
Laboratory of Molecular Immunoregulation, National Cancer Institute-
Frederick Cancer Research Facility 21701.
The effects of transforming growth factor beta 1 or beta 2 (TGF-beta 1 or
-beta 2) on the in vitro proliferation and differentiation of normal and
malignant human hematopoietic cells were studied. Both forms of TGF- beta
suppressed both the normal cellular proliferation and colony formation
induced by recombinant human interleukin-3 (IL-3) and
granulocyte-macrophage colony-stimulating factor (GM-CSF). In the presence
of GM-CSF or IL-3, optimal concentrations of TGF-beta (400 pmol/L)
inhibited colony formation by erythroid (BFU-E), multipotential (CFU-GEMM),
and granulocyte-macrophage (CFU-GM) progenitor cells by 90% to 100%,
whereas granulocyte or monocyte cluster formation was not inhibited. In
contrast, neither form of TGF-beta had any effect on G- CSF-induced
hematopoiesis. The suppressive action appeared to be mediated directly by
TGF-beta since antiproliferative responses were also observed in accessory
cell-depleted bone marrow cells. In contrast to normal bone marrow cells,
both GM- and G-CSF-induced proliferation of cells from patients with
chronic myelogenous leukemia were suppressed in a dose-dependent manner by
TGF-beta. Differential effects of TGF-beta on the proliferation of
established leukemic lines were also observed since most cell lines of
myelomonocytic nature studied were strongly inhibited where erythroid cell
lines were either insensitive or poorly inhibited by TGF-beta. These
results suggest that TGF-beta is an important modulator of human
hematopoiesis that selectively regulates the growth of less mature
hematopoietic cell populations with a high proliferative capacity as
opposed to more differentiated cells, which are not affected by TGF-beta.
Volume 72,
Issue 5,
pp. 1504-1511,
11/01/1988
Copyright © 1988 by The American Society of Hematology

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