|
|
Blood, 1 October 2006, Vol. 108, No. 7, pp. 2349-2357.
Prepublished online as a Blood First Edition Paper on June 8, 2006; DOI 10.1182/blood-2004-08-009498.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Oncogenic NRAS rapidly and efficiently induces CMML- and AML-like diseases in mice
Chaitali Parikh,
Ramesh Subrahmanyam, and
Ruibao Ren
From the Rosenstiel Basic Medical Sciences Research Center, Department of Biology; and the Graduate Program in Biophysics and Structural Biology, Department of Biochemistry, Brandeis University, Waltham, MA.
Activating mutations in RAS, predominantly NRAS, are common in myeloid malignancies. Previous studies in animal models have shown that oncogenic NRAS is unable to induce myeloid malignancies effectively, and it was suggested that oncogenic NRAS might only act as a secondary mutation in leukemogenesis. In this study, we examined the leukemogenicity of NRAS using an improved mouse bone marrow transduction and transplantation model. We found that oncogenic NRAS rapidly and efficiently induced chronic myelomonocytic leukemia (CMML)– or acute myeloid leukemia (AML)– like disease in mice, indicating that mutated NRAS can function as an initiating oncogene in the induction of myeloid malignancies. In addition to CMML and AML, we found that NRAS induced mastocytosis in mice. This result indicates that activation of the RAS pathway also plays an important role in the pathogenesis of mastocytosis. The mouse model for NRAS leukemogenesis established here provides a system for further studying the molecular mechanisms in the pathogenesis of myeloid malignancies and for testing relevant therapies.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Zuber, I. Radtke, T. S. Pardee, Z. Zhao, A. R. Rappaport, W. Luo, M. E. McCurrach, M.-M. Yang, M. E. Dolan, S. C. Kogan, et al.
Mouse models of human AML accurately predict chemotherapy response
Genes & Dev.,
April 1, 2009;
23(7):
877 - 889.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-I. Kim, I. Matise, M. D. Diers, and D. A. Largaespada
RAS oncogene suppression induces apoptosis followed by more differentiated and less myelosuppressive disease upon relapse of acute myeloid leukemia
Blood,
January 29, 2009;
113(5):
1086 - 1096.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Case, E. Matheson, L. Minto, R. Hassan, C. J. Harrison, N. Bown, S. Bailey, J. Vormoor, A. G. Hall, and J. A.E. Irving
Mutation of Genes Affecting the RAS Pathway Is Common in Childhood Acute Lymphoblastic Leukemia
Cancer Res.,
August 15, 2008;
68(16):
6803 - 6809.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Quinlan, S. E. Quatela, M. R. Philips, and J. Settleman
Activated Kras, but Not Hras or Nras, May Initiate Tumors of Endodermal Origin via Stem Cell Expansion
Mol. Cell. Biol.,
April 15, 2008;
28(8):
2659 - 2674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-J. Zhang, L.-Y. Ma, Q.-H. Huang, G. Li, B.-W. Gu, X.-D. Gao, J.-Y. Shi, Y.-Y. Wang, L. Gao, X. Cai, et al.
Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia
PNAS,
February 12, 2008;
105(6):
2076 - 2081.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Parikh, R. Subrahmanyam, and R. Ren
Oncogenic NRAS, KRAS, and HRAS Exhibit Different Leukemogenic Potentials in Mice
Cancer Res.,
August 1, 2007;
67(15):
7139 - 7146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
