|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 October 2001, Vol. 98, No. 8, pp. 2308-2318
PLENARY PAPER
Estrogen-dependent E2a/Pbx1 myeloid cell lines exhibit
conditional differentiation that can be arrested by other leukemic
oncoproteins
David B. Sykes and
Mark P. Kamps
From the Department of Molecular Pathology, University
of California San Diego School of Medicine, La Jolla.
The molecular pathways of normal myeloid differentiation, as well
as the mechanisms by which oncogenes disrupt this process, remain
poorly understood. A major limitation in approaching this problem has
been the lack of suitable cell lines that exhibit normal, terminal, and
synchronous differentiation in the absence of endogenous oncoproteins
and in response to physiologic cytokines, and whose differentiation can
be arrested by ectopically expressed human oncoproteins. This report
describes clonal, granulocyte-macrophage colony-stimulating
factor-dependent myeloid cell lines that exhibit these properties. The
cell lines were established by conditional immortalization of primary
murine marrow progenitors with an estrogen-regulated E2a/Pbx1-estrogen
receptor fusion protein. Clones were identified that proliferated as
immortalized blasts in the presence of estrogen, and that exhibited
granulocytic, monocytic, or bipotential (granulocytic and monocytic)
differentiation on estrogen withdrawal. Differentiation was normal and
terminal as evidenced by morphology, cell surface markers, gene
expression, and functional assays. The differentiation of the cells
could be arrested by heterologous oncoproteins including AML1/ETO,
PML/RAR , PLZF/RAR, Nup98/HoxA9, and other Hox proteins. Furthermore, the study examined the effects of cooperating oncoproteins such as Ras or Bcr/Abl, which allowed for both factor-independent proliferation and differentiation, or Bcl-2, which permitted
factor-independent survival but not proliferation. These myeloid cell
lines provide tools for examining the biochemical and genetic
pathways that accompany normal differentiation as well as a system in
which to dissect how other leukemic oncoproteins interfere with these pathways.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Methot, D. Guay, J. Rubin, D. Ethier, K. Ortega, S. Wong, D. Normandin, C. Beaulieu, T. J. Reddy, D. Riendeau, et al.
In Vivo Inhibition of Serine Protease Processing Requires a High Fractional Inhibition of Cathepsin C
Mol. Pharmacol.,
June 1, 2008;
73(6):
1857 - 1865.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Methot, J. Rubin, D. Guay, C. Beaulieu, D. Ethier, T. J. Reddy, D. Riendeau, and M. D. Percival
Inhibition of the Activation of Multiple Serine Proteases with a Cathepsin C Inhibitor Requires Sustained Exposure to Prevent Pro-enzyme Processing
J. Biol. Chem.,
July 20, 2007;
282(29):
20836 - 20846.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Odegaard, D. Vats, L. Zhang, R. Ricardo-Gonzalez, K. L. Smith, D. B. Sykes, M. P. Kamps, and A. Chawla
Quantitative expansion of ES cell-derived myeloid progenitors capable of differentiating into macrophages
J. Leukoc. Biol.,
March 1, 2007;
81(3):
711 - 719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. G. Wang, M. P. Pasillas, and M. P. Kamps
Meis1 programs transcription of FLT3 and cancer stem cell character, using a mechanism that requires interaction with Pbx and a novel function of the Meis1 C-terminus
Blood,
July 1, 2005;
106(1):
254 - 264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zhang and A. Varki
Cell surface sialic acids do not affect primary CD22 interactions with CD45 and surface IgM nor the rate of constitutive CD22 endocytosis
Glycobiology,
November 1, 2004;
14(11):
939 - 949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Sykes and M. P. Kamps
E2a/Pbx1 Induces the Rapid Proliferation of Stem Cell Factor-Dependent Murine Pro-T Cells That Cause Acute T-Lymphoid or Myeloid Leukemias in Mice
Mol. Cell. Biol.,
February 1, 2004;
24(3):
1256 - 1269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Welch, L. Escoubet-Lozach, D. B. Sykes, K. Liddiard, D. R. Greaves, and C. K. Glass
TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-dependent Mechanism
J. Biol. Chem.,
November 1, 2002;
277(45):
42821 - 42829.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
