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The production of transforming growth factor-beta in acute megakaryoblastic
leukemia and its possible implications in myelofibrosis
T Terui, Y Niitsu, K Mahara, Y Fujisaki, Y Urushizaki, Y Mogi, Y Kohgo, N Watanabe, M Ogura and H Saito
Department of Internal Medicine (Section 4), Sapporo Medical College,
Japan.
Acute myelofibrosis is often associated with acute megakaryoblastic
leukemia (AMKBL). Although the exact mechanism for the progression of
myelofibrosis in AMKBL is unclear, certain humoral factors from
megakaryoblastic cells, the precursors of platelets, may be involved in the
enhancement of collagen synthesis by bone marrow fibroblasts. The present
study, therefore, is an investigation of the possible pathogenic role of
transforming growth factor-beta (TGF-beta), known to be a very potent
collagen-stimulating factor found in platelets in the myelofibrosis of
AMKBL. The results obtained were as follows: (1) Conditioned media from
peripheral megakaryoblasts taken from an AMKBL patient and from established
megakaryoblast cell lines (MEG-01) had much greater stimulatory effects on
collagen synthesis in bone marrow fibroblasts than conditioned media from
other leukemic cell types. (2) Based on an assessment of soft agar colony
formation, there was greater TGF-beta activity in media that had been
conditioned from megakaryoblasts than in media from other leukemic cell
types. (3) When compared with other leukemic-cell types, megakaryoblasts
showed substantially greater expression of TGF-beta mRNA that was
hybridized at 2.5 kb with a TGF-beta cDNA probe, and TGF-beta polypeptides
were detected at 13 Kd with anti-TGF-beta antibodies. (4) The addition of
the anti-TGF-beta antibody inhibited the stimulatory effects of the
megakaryoblast conditioned medium on collagen synthesis in bone marrow
fibroblasts. These results clearly suggest that megakaryoblasts produce and
secrete an active form of TGF-beta and stimulate collagen synthesis in bone
marrow fibroblasts in a paracrine manner.
Volume 75,
Issue 7,
pp. 1540-1548,
04/01/1990
Copyright © 1990 by The American Society of Hematology
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