|
|
Prepublished online as a Blood First Edition Paper on October 17, 2002; DOI 10.1182/blood-2002-08-2635.
Previous Article | Table of Contents | Next Article 
Blood, 1 March 2003, Vol. 101, No. 5, pp. 1984-1986
NEOPLASIA
Brief report
Leukemic potential of doubly mutant Nf1 and
Wv hematopoietic cells
David A. Ingram,
Mary Jo Wenning,
Kevin Shannon, and
D. Wade Clapp
From the Indiana University School of Medicine, Herman
B. Wells Center for Pediatric Research, Department of
Microbiology/Immunology, Indianapolis, IN; and University of California
at San Francisco, Department of Pediatrics, San Francisco, CA.
The development of molecularly targeted treatments of adult
leukemias warrants investigation of these targets in similar pediatric leukemias. The NF1 tumor suppressor gene, which encodes a
GTPase activating protein for p21ras, is frequently
inactivated in juvenile myelomonocytic leukemia (JMML). Other patients
with JMML acquire activating RAS gene mutations. Recipient
mice reconstituted with Nf1 / fetal
hematopoietic cells develop a myeloproliferative disease (MPD) that
models the human disease. JMML arises from clonal expansion of a
hematopoietic stem cell, and JMML cells and murine
Nf1 / hematopoietic cells are hypersensitive
to granulocyte macrophage-colony stimulating factor and KitL, the
ligand for c-kit. We generated embryos doubly mutant for the
Wv allele of c-kit and Nf1 to ask
if reduction of c-kit activity would delay or prevent the development
of MPD. Despite a reduction in c-kit activity to approximately 10% of
wild-type levels,
Nf1 / ;Wv/Wv
cells induced MPD in recipient mice.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
L. S. Haneline, H. White, F.-C. Yang, S. Chen, C. Orschell, R. Kapur, and D. A. Ingram
Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive repopulating ability of hematopoietic stem cells in vivo
Blood,
February 15, 2006;
107(4):
1375 - 1382.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Illmer, C. Thiede, A. Fredersdorf, S. Stadler, A. Neubauer, G. Ehninger, and M. Schaich
Activation of the RAS Pathway Is Predictive for a Chemosensitive Phenotype of Acute Myelogenous Leukemia Blasts
Clin. Cancer Res.,
May 1, 2005;
11(9):
3217 - 3224.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Zhu, G. Saberwal, Y. Lu, L. C. Platanias, and E. A. Eklund
The Interferon Consensus Sequence-binding Protein Activates Transcription of the Gene Encoding Neurofibromin 1
J. Biol. Chem.,
December 3, 2004;
279(49):
50874 - 50885.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Hiatt, D. A. Ingram, H. Huddleston, D. F. Spandau, R. Kapur, and D. W. Clapp
Loss of the Nf1 Tumor Suppressor Gene Decreases Fas Antigen Expression in Myeloid Cells
Am. J. Pathol.,
April 1, 2004;
164(4):
1471 - 1479.
[Abstract]
[Full Text]
[PDF]
|
 |
|
| |