|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 475-482
Deregulated E2F-1 blocks terminal differentiation and loss of
leukemogenicity of M1 myeloblastic leukemia cells without
abrogating induction of p15INK4B and
p16INK4A
Arshad Amanullah,
Barbara Hoffman, and
Dan A. Liebermann
From the Fels Institute for Cancer Research and Molecular
Biology and Department of Biochemistry, Temple University School
of Medicine; and Cell and Molecular Biology Graduate Group, University
of Pennsylvania, Philadelphia, PA.
The transcription factor E2F-1 has been postulated to play a crucial
role in the control of cell cycle progression because of its ability to
be bound and regulated by the retinoblastoma gene product (pRb).
Exogenous expression of E2F-1, under growth restrictive conditions, was
shown to result in p53-dependent programmed cell death. The
consequences of deregulated expression of E2F-1 on terminal
differentiation of hematopoietic cells in the absence of
E2F-1-mediated apoptosis, as well as mechanistic insights into how
deregulated E2F-1 may affect terminal differentiation, have not been
established. The autonomously proliferating M1 myeloblastic leukemia
cell line, which is null for p53 expression and can be induced by
interleukin-6 (IL-6) to undergo terminal macrophage differentiation
with concomitant loss of leukemogenicity, provides a particularly
attractive model system to address these issues. Deregulated and
continued expression of E2F-1 blocked the IL-6-induced terminal
differentiation program at an early blast stage, giving rise to
immature cells, which continued to proliferate without undergoing
apoptosis and retained their leukemogenic phenotype. Although E2F-1
blocked IL-6-mediated terminal differentiation and its associated
growth arrest, it did not prevent the rapid induction of both
p15INK4B and p16INK4A, inhibition of cdk4
kinase activity, and subsequent hypophosphorylation of pRb. The results
obtained imply that genetic alterations that both impair p53 function
and deregulate E2F-1 expression may render hematopoietic cells
refractory to the induction of differentiation and are, thereby, likely
to play a major role in the progression of leukemias.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. Zhou, L. Zhang, A. Wang, B. Song, K. Gong, L. Zhang, M. Hu, X. Zhang, N. Zhao, and Y. Gong
The Association of GSK3{beta} with E2F1 Facilitates Nerve Growth Factor-induced Neural Cell Differentiation
J. Biol. Chem.,
May 23, 2008;
283(21):
14506 - 14515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Kikuchi, R. Shimizu, T. Wada, H. Ando, M. Nakamura, K. Ozawa, and Y. Furukawa
E2F-6 Suppresses Growth-Associated Apoptosis of Human Hematopoietic Progenitor Cells by Counteracting Proapoptotic Activity of E2F-1
Stem Cells,
October 1, 2007;
25(10):
2439 - 2447.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mohty, A. S. M. Yong, R. M. Szydlo, J. F. Apperley, and J. V. Melo
The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia
Blood,
July 1, 2007;
110(1):
380 - 383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Markus, M. T. Garin, J. Bies, N. Galili, A. Raza, M. J. Thirman, M. M. Le Beau, J. D. Rowley, P. P. Liu, and L. Wolff
Methylation-Independent Silencing of the Tumor Suppressor INK4b (p15) by CBF{beta}-SMMHC in Acute Myelogenous Leukemia with inv(16)
Cancer Res.,
February 1, 2007;
67(3):
992 - 1000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Schmidt, J. Bies, T. Tamura, K. Ozato, and L. Wolff
The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15Ink4b in murine myeloid cells
Blood,
June 1, 2004;
103(11):
4142 - 4149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Efimova, O. Martinez, A. Lokshin, T. Arima, and B. S. Prabhakar
IG20, a MADD Splice Variant, Increases Cell Susceptibility to {gamma}-Irradiation and Induces Soluble Mediators That Suppress Tumor Cell Growth
Cancer Res.,
December 15, 2003;
63(24):
8768 - 8776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. D'Alo', L. M. Johansen, E. A. Nelson, H. S. Radomska, E. K. Evans, P. Zhang, C. Nerlov, and D. G. Tenen
The amino terminal and E2F interaction domains are critical for C/EBP{alpha}-mediated induction of granulopoietic development of hematopoietic cells
Blood,
November 1, 2003;
102(9):
3163 - 3171.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Scheijen, M. Bronk, T. van der Meer, and R. Bernards
Constitutive E2F1 Overexpression Delays Endochondral Bone Formation by Inhibiting Chondrocyte Differentiation
Mol. Cell. Biol.,
May 15, 2003;
23(10):
3656 - 3668.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
