|
|
Blood, 15 October 2003, Vol. 102, No. 8, pp. 2976-2984.
Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-05-1550.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Evidence for a positive role of SHIP in the BCR-ABL–mediated transformation of primitive murine hematopoietic cells and in human chronic myeloid leukemia
Xiaoyan Jiang,
Matthew Stuible,
Yves Chalandon,
Andra Li,
Wing Yiu Chan,
Wolfgang Eisterer,
Gerald Krystal,
Allen Eaves, and
Connie Eaves
From the Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver; and the Departments of Medical Genetics, Pathology and Laboratory Medicine, and Medicine, University of British Columbia, Vancouver, BC, Canada.
Previous studies suggested that the SH2-containing inositol-5-phosphatase (SHIP) may play a tumor suppressor-like function in BCR-ABL–mediated leukemogenesis. To investigate this possibility, we first developed a new assay for quantitating transplantable multilineage leukemia-initiating cells (L-ICs) in hematopoietic stem cell (HSC)–enriched mouse bone marrow (BM) cells transduced with a BCR-ABL–GFP (green fluorescent protein) retrovirus. The frequency of L-ICs (1 of 430 Sca-1+lin– cells) was 7-fold lower than the frequency of HSCs in the Sca-1+lin– subset transduced with a control virus (1 of 65 cells). Forced BCRABL expression was also accompanied by a loss of regular HSC activity consistent with the acquisition of an increased probability of differentiation. Interestingly, the frequency and in vivo behavior of wild-type (+/+) and SHIP–/– L-ICs were indistinguishable, and in vitro, Sca-1+lin– BCR-ABL–transduced SHIP–/– cells showed a modestly reduced factor independence. Comparison of different populations of cells from patients with chronic myeloid leukemia (CML) in chronic phase and normal human BM showed that the reduced expression of full-length SHIP proteins seen in the more mature (CD34–lin+) leukemic cells is not mirrored in the more primitive (CD34+lin–) leukemic cells. Thus, SHIP expression appears to be differently altered in the early and late stages of differentiation of BCR-ABL–transformed cells, underscoring the importance of the cellular context in which its mechanistic effects are analyzed.
 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]
|
|
|
|
|
|
|
H. G. Jorgensen, M. Copland, E. K. Allan, X. Jiang, A. Eaves, C. Eaves, and T. L. Holyoake
Intermittent Exposure of Primitive Quiescent Chronic Myeloid Leukemia Cells to Granulocyte-Colony Stimulating Factor In vitro Promotes their Elimination by Imatinib Mesylate
Clin. Cancer Res.,
January 15, 2006;
12(2):
626 - 633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Kharas and D. A. Fruman
ABL Oncogenes and Phosphoinositide 3-Kinase: Mechanism of Activation and Downstream Effectors
Cancer Res.,
March 15, 2005;
65(6):
2047 - 2053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Chen, M. Levis, P. Brown, K.-T. Kim, J. Allebach, and D. Small
FLT3/ITD Mutation Signaling Includes Suppression of SHP-1
J. Biol. Chem.,
February 18, 2005;
280(7):
5361 - 5369.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Moody, L. Xu, C. D. Helgason, and F. R. Jirik
Anemia, thrombocytopenia, leukocytosis, extramedullary hematopoiesis, and impaired progenitor function in Pten+/-SHIP-/- mice: a novel model of myelodysplasia
Blood,
June 15, 2004;
103(12):
4503 - 4510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Jiang, Y. Zhao, W.-Y. Chan, S. Vercauteren, E. Pang, S. Kennedy, F. Nicolini, A. Eaves, and C. Eaves
Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia
Blood,
May 15, 2004;
103(10):
3897 - 3904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
