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Next Article 
Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3001-3009
PLENARY PAPER
Modulation of bcl-2 and p27 in human primitive proliferating
hematopoietic progenitors by autocrine TGF- 1 is a cell
cycle-independent effect and influences their hematopoietic potential
Luca Pierelli,
Maria Marone,
Giuseppina Bonanno,
Simona Mozzetti,
Sergio Rutella,
Roberta Morosetti,
Carlo Rumi,
Salvatore Mancuso,
Giuseppe Leone, and
Giovanni Scambia
From the Cattedra di Ematologia, Istituto di Ostetricia e
Ginecologia, Universita' Cattolica del Sacro Cuore, Rome, Italy.
Primitive, proliferating hematopoietic progenitors (defined as
cytokine low-responding primitive progenitors; CLRPP), isolated from
human CD34+ cells, expressed endoglin (CD105) and produced transforming growth factor- 1 (TGF-1). Culture of CLRPP in
serum-free conditions with anti-TGF-1 monoclonal antibody produced a
substantial decrease in bcl-2 protein/RNA levels and a significant
reduction of cloning and long-term culture-initiating cell (LTC-IC)
activities. GATA-1 and PU.1 RNA levels were significantly up-regulated
in anti-TGF-1-treated CLRPP, which generated an increased number of
cells expressing CD15/CD11b/glycophorin-A. The described effects of
TGF-1 neutralization were observed in the absence of any relevant effect on cell cycle; number of cell divisions; p53, c-myc, and p21 RNA
levels; bcl-xL and bax protein levels; and c-myc/p16/p21/p107/Rb cell
cycle-related protein levels. A relevant increase in p27 protein
levels was observed in anti-TGF-1-treated CLRPP, suggesting a role
for p27 in the regulation of the hematopoietic potential. The present
study on human progenitors and previously reported data on TGF-1
knockout mice suggest that, at the autocrine level, the cell cycle
inhibitor TGF-1 plays an important role in regulating the survival
and differentiation of primitive proliferating hematopoietic progenitors by cell cycle-independent mechanisms.
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