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Characteristics of bone marrow fibroblast colony-forming cells (CFU-F) and
their progeny in patients with myeloproliferative disorders
H Castro-Malaspina, RE Gay, SC Jhanwar, JA Hamilton, DR Chiarieri, PA Meyers, S Gay and MA Moore
Chronic myeloproliferative disorders (MPD) are clonal diseases of the
pluripotent hematopoietic stem cell frequently associated with
myelofibrosis (MF). There is only indirect evidence indicating that the
increased deposition of collagen in bone marrow matrix is a secondary
phenomenon. A liquid culture system for cloning and growing bone marrow
fibroblasts has permitted us to approach more directly the understanding of
the pathogenesis of myelofibrosis by comparing the biophysical, growth, and
functional characteristics of fibroblasts from normals, MPD patients
without MF, and those with MF. In patients with MF, marrow fibroblast
colony (CFU-F) formation could not be studied; fibroblasts were grown from
marrow explants. CFU-E from normals and MPD patients exhibited similar cell
density distribution and similar cell sedimentation rates. These
similarities contrasted sharply with the differences seen when the
erythroid and granulocyte-macrophage progenitors were studied by the same
methods. There was a marked light density shift and a rapidly sedimenting
shift of MPD hematopoietic colony-forming cells. Marrow fibroblasts from
MPD patients with and without MF displayed the same in vitro growth
characteristics as fibroblasts from normals. Both types of fibroblasts
exhibited anchorage and serum dependence, and contact inhibition of growth.
Marrow fibroblasts were also characterized for the presence and
distribution of fibronectin and collagen types by immunofluorescent
staining using monospecific antibodies. Extracellular matrix, membrane-,
and cytoplasm- associated fibronectin, type I, type III, and type V
collagen showed a similar staining pattern in both normal and myelofibrotic
marrow fibroblasts. Plasminogen-dependent fibrinolytic activity elicited
from normal and myelofibrotic marrow fibroblasts were equivalent.
Chromosomal analysis of hematopoietic cells and marrow fibroblasts from
Philadelphia chromosome positive chronic myelocytic leukemia patients with
and without MF showed that the Philadelphia chromosome was present only in
hematopoietic cells. The results of these studies taken together
demonstrate that bone marrow collagen-producing cells from MPD patients
with and without MF behave in vitro as do those from normals. These
findings support the hypothesis that that the marrow fibrosis observed in
patients with MPD results from a reactive process rather than from a
primary disorder affecting the marrow collagen-producing cells.
Volume 59,
Issue 5,
pp. 1046-1054,
05/01/1982
Copyright © 1982 by The American Society of Hematology
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