Abstract
Cultures of purified hemopoietic stem cells transduced with an activated mutant of M-Ras contained abnormal cells that, despite the presence of only low levels of growth factors, generated large, dense colonies of macrophages and blast cells. Cells from these colonies survived and grew continuously in the absence of growth factors and generated clonal cell-lines that were mainly composed of well-differentiated mast cells, with a low frequency of undifferentiated cells. When transplanted into sublethally irradiated syngeneic mice, four out of four such clones gave rise to a systemic mastocytosis and mast-cell leukemia. However, the donor clones also generated low percentages of cells with the morphological and cell-surface characteristics of erythrocytes, granulocytes, monocytes and T- and B-lymphocytes. These data indicate that signals downstream of activated M-Ras are sufficient to transform hemopoietic stem cells, and while preserving their capacity to generate other cell-lineages in vivo, result in preferential generation of mast cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Akin C, Kirshenbaum AS, Semere T, Worobec AS, Scott LM, Metcalfe DD . (2000). Exp Hematol 28: 140–147.
Christensen JL, Weissman IL . (2001). Proc Natl Acad Sci USA 98: 14541–14546.
Cortez D, Stoica G, Pierce JH, Pendergast AM . (1996). Oncogene 13: 2589–2594.
Drachman JG . (2000). Curr Opin Hematol 7: 183–190.
Ehrhardt A, David MD, Ehrhardt GR, Schrader JW . (2004). Mol Cell Biol 24: 6311–6323.
Ehrhardt A, Ehrhardt GR, Guo X, Schrader JW . (2002). Exp Hematol 30: 1089–1106.
Ehrhardt GR, Leslie KB, Lee F, Wieler JS, Schrader JW . (1999). Blood 94: 2433–2444.
Guo X, Gerl RE, Schrader JW . (2003). J Biol Chem 278: 22237–22242.
Guo X, Schrader KA, Xu Y, Schrader JW . (2005). Oncogene 24: 2330–2342.
Hu ZQ, Kobayashi K, Zenda N, Shimamura T . (1997). Blood 89: 526–533.
Jiang X, Ng E, Yip C, Eisterer W, Chalandon Y, Stuible M et al. (2002). Blood 100: 3731–3740.
Kimmelman A, Tolkacheva T, Lorenzi MV, Osada M, Chan AM . (1997). Oncogene 15: 2675–2685.
Kitamura Y, Go S . (1979). Blood 53: 492–497.
Louahed J, Grasso L, De Smet C, Van Roost E, Wildmann C, Nicolaides NC et al. (1999). Blood 94: 1701–1710.
Ohba Y, Mochizuki N, Yamashita S, Chan AM, Schrader JW, Hattori S et al. (2000). J Biol Chem 275: 20020–20026.
Passegue E, Jamieson CH, Ailles LE, Weissman IL . (2003). Proc Natl Acad Sci USA 100(Suppl 1): 11842–11849.
Wang D, Yang W, Du J, Devalaraja MN, Liang P, Matsumoto K et al. (2000). Oncogene 19: 4647–4659.
Ward KR, Zhang KX, Somasiri AM, Roskelley CD, Schrader JW . (2004). Oncogene 23: 1187–1196.
Yang J, Chatterjee-Kishore M, Staugaitis SM, Nguyen H, Schlessinger K, Levy DE et al. (2005). Cancer Res 65: 939–947.
Zhang KX, Ward KR, Schrader JW . (2004). Mol Cancer Res 2: 242–255.
Acknowledgements
We thank Andy Johnson for fluorescence-activated cell sorting; Lea Wong and Samantha Kleczkowski for animal care. This work was supported by grants from The Canadian Institute of Health Research.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guo, X., Stratton, L. & Schrader, J. Expression of activated M-Ras in hemopoietic stem cells initiates leukemogenic transformation, immortalization and preferential generation of mast cells. Oncogene 25, 4241–4244 (2006). https://doi.org/10.1038/sj.onc.1209452
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209452