|
|
Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2001-11-0089.
 Previous Article | Table of Contents | Next Article 
Blood, 15 October 2002, Vol. 100, No. 8, pp. 2989-2995
NEOPLASIA
PML-RAR induces promyelocytic leukemias with high efficiency
following retroviral gene transfer into purified murine
hematopoietic progenitors
Saverio Minucci,
Silvia Monestiroli,
Sabrina Giavara,
Simona Ronzoni,
Francesco Marchesi,
Alessandra Insinga,
Daniela Diverio,
Patrizia Gasparini,
Manuela Capillo,
Emanuela Colombo,
Cristian Matteucci,
Francesco Contegno,
Francesco Lo-Coco,
Eugenio Scanziani,
Alberto Gobbi, and
Pier Giuseppe Pelicci
From the European Institute of Oncology, Department of
Experimental Oncology, Milan, Italy; Department of Physiology and
General Biochemistry, and Department of Veterinary Pathology, Hygiene
and Public Health, School of Veterinary Medicine, University of Milan,
Italy; IFOM-FIRC Institute of Molecular Oncology, Milan, Italy; and
Department of Human Biotechnology and Hematology, University of Rome
"La Sapienza," Rome, Italy.
Acute promyelocytic leukemia (APL) is associated with chromosomal
translocations resulting in fusion proteins of the retinoic acid
receptor (RAR). Here, we report a novel murine model system for APL,
based on the transduction of purified murine hematopoietic progenitors
(lin ) using high-titer retroviral vectors encoding
promyelocytic leukemia-RAR (PML-RAR), and the green
fluorescent protein (GFP) as a marker. PML-RAR-expressing
lin cells were impaired in their ability to undergo
terminal myeloid differentiation and showed increased proliferative
potential in vitro. Inoculation of transduced lin cells
into syngeneic, irradiated mice resulted in the development of retinoic
acid-sensitive promyelocytic leukemias at high frequency (> 80%) and
short latency (approximately 4 months). Morphologic and
immunophenotypic analysis revealed no gross abnormalities of the
preleukemic bone marrows. However, hematopoietic progenitors from
PML-RAR preleukemic mice showed a severe impairment in their ability to
undergo myeloid differentiation in vitro. This result, together with
the monoclonality or oligoclonality of the leukemic blasts, supports a
"multiple-hit" model, where the fusion protein causes a
"preleukemic" phase, and leukemia occurs after additional genetic
lesions. This model system faithfully reproduces the main characteristics of human APL and represents a versatile tool for the in
vitro and in vivo study of mechanisms of leukemogenesis and the
design of protocols for differentiation treatment.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Radaelli, F. Marchesi, V. Patton, and E. Scanziani
Diagnostic Exercise: Sudden Death in a Mouse with Experimentally Induced Acute Myeloid Leukemia
Vet. Pathol.,
November 1, 2009;
46(6):
1301 - 1305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Morey, C. Brenner, F. Fazi, R. Villa, A. Gutierrez, M. Buschbeck, C. Nervi, S. Minucci, F. Fuks, and L. Di Croce
MBD3, a Component of the NuRD Complex, Facilitates Chromatin Alteration and Deposition of Epigenetic Marks
Mol. Cell. Biol.,
October 1, 2008;
28(19):
5912 - 5923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Hoemme, A. Peerzada, G. Behre, Y. Wang, M. McClelland, K. Nieselt, M. Zschunke, C. Disselhoff, S. Agrawal, F. Isken, et al.
Chromatin modifications induced by PML-RAR{alpha} repress critical targets in leukemogenesis as analyzed by ChIP-Chip
Blood,
March 1, 2008;
111(5):
2887 - 2895.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. van Wageningen, M. C. Breems-de Ridder, J. Nigten, G. Nikoloski, C. A. J. Erpelinck-Verschueren, B. Lowenberg, T. de Witte, D. G. Tenen, B. A. van der Reijden, and J. H. Jansen
Gene transactivation without direct DNA binding defines a novel gain-of-function for PML-RAR{alpha}
Blood,
February 1, 2008;
111(3):
1634 - 1643.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. T. Chan, J. L. Kutok, I. R. Williams, S. Cohen, S. Moore, H. Shigematsu, T. J. Ley, K. Akashi, M. M. Le Beau, and D. G. Gilliland
Oncogenic K-ras cooperates with PML-RAR{alpha} to induce an acute promyelocytic leukemia-like disease
Blood,
September 1, 2006;
108(5):
1708 - 1715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. B. Kindle, P. J. F. Troke, H. M. Collins, S. Matsuda, D. Bossi, C. Bellodi, E. Kalkhoven, P. Salomoni, P. G. Pelicci, S. Minucci, et al.
MOZ-TIF2 Inhibits Transcription by Nuclear Receptors and p53 by Impairment of CBP Function
Mol. Cell. Biol.,
February 1, 2005;
25(3):
988 - 1002.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Lane and T. J. Ley
Neutrophil Elastase Is Important for PML-Retinoic Acid Receptor {alpha} Activities in Early Myeloid Cells
Mol. Cell. Biol.,
January 1, 2005;
25(1):
23 - 33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zheng, T. Beissert, N. Kukoc-Zivojnov, E. Puccetti, J. Altschmied, C. Strolz, S. Boehrer, H. Gul, O. Schneider, O. G. Ottmann, et al.
{gamma}-Catenin contributes to leukemogenesis induced by AML-associated translocation products by increasing the self-renewal of very primitive progenitor cells
Blood,
May 1, 2004;
103(9):
3535 - 3543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Westervelt, A. A. Lane, J. L. Pollock, K. Oldfather, M. S. Holt, D. B. Zimonjic, N. C. Popescu, J. F. DiPersio, and T. J. Ley
High-penetrance mouse model of acute promyelocytic leukemia with very low levels of PML-RAR{alpha} expression
Blood,
September 1, 2003;
102(5):
1857 - 1865.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
