|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 2132-2137
Granulocyte colony-stimulating factor receptor mutations in severe
congenital neutropenia transforming to acute myelogenous leukemia
confer resistance to apoptosis and enhance cell survival
Melissa G. Hunter and
Belinda R. Avalos
From the Molecular, Cellular, and Developmental Biology Program and
the Bone Marrow Transplantation Program, The Ohio State University,
Arthur G. James Cancer Hospital & Research Institute, Columbus, OH.
Patients with severe congenital neutropenia (SCN) are at increased
risk for the development of acute myelogenous leukemia (AML). In the
subset of patients with SCN that progresses to AML, acquired mutations
in the receptor for granulocyte colony-stimulating factor (G-CSF) have
been detected that result in the expression of truncated forms of the
G-CSF receptor (G-CSFR) protein. G-CSFR truncation mutants from these
patients trans-duce hyperproliferative growth responses. In this paper,
we show that the most frequently isolated mutant G-CSFR form from
patients with SCN/AML ( 716) confers resistance to apoptosis and
prolongs cell survival through a mechanism involving Akt, a downstream
target of PI3-kinase. G-CSF stimulation of cells expressing the G-CSFR
truncation mutant induces sustained activation of Akt and prolonged
phosphorylation of the pro-apoptotic protein Bad, resulting in enhanced
cell survival. Extension of cell survival allowing for sufficient time
for the acquisition of additional oncogenic events may represent an
important mechanism by which G-CSFR mutations contribute to
leukemogenesis. These data provide further insight into the
pathophysiologic contribution of G-CSFR mutations to AML.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Berliner
Lessons from congenital neutropenia: 50 years of progress in understanding myelopoiesis
Blood,
June 15, 2008;
111(12):
5427 - 5432.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Link, G. Kunter, Y. Kasai, Y. Zhao, T. Miner, M. D. McLellan, R. E. Ries, D. Kapur, R. Nagarajan, D. C. Dale, et al.
Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia
Blood,
September 1, 2007;
110(5):
1648 - 1655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Germeshausen, M. Ballmaier, and K. Welte
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: results of a long-term survey
Blood,
January 1, 2007;
109(1):
93 - 99.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Sloand, A. S. M. Yong, S. Ramkissoon, E. Solomou, T. C. Bruno, S. Kim, M. Fuhrer, S. Kajigaya, A. J. Barrett, and N. S. Young
Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor
PNAS,
September 26, 2006;
103(39):
14483 - 14488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, et al.
The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy
Blood,
June 15, 2006;
107(12):
4628 - 4635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zhuang, Y. Qiu, S. C. Kogan, and F. Dong
Increased CCAAT Enhancer-binding Protein {epsilon} (C/EBP{epsilon}) Expression and Premature Apoptosis in Myeloid Cells Expressing Gfi-1 N382S Mutant Associated with Severe Congenital Neutropenia
J. Biol. Chem.,
April 21, 2006;
281(16):
10745 - 10751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Liu, Y. Qiu, L. Xiao, and F. Dong
Involvement of Protein Kinase C{epsilon} in the Negative Regulation of Akt Activation Stimulated by Granulocyte Colony-Stimulating Factor
J. Immunol.,
February 15, 2006;
176(4):
2407 - 2413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zhuang, Y. Qiu, S. J. Haque, and F. Dong
Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1
J. Leukoc. Biol.,
October 1, 2005;
78(4):
1008 - 1015.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Hunter, A. Jacob, L. C. O'Donnell, A. Agler, L. J. Druhan, K. M. Coggeshall, and B. R. Avalos
Loss of SHIP and CIS Recruitment to the Granulocyte Colony-Stimulating Factor Receptor Contribute to Hyperproliferative Responses in Severe Congenital Neutropenia/Acute Myelogenous Leukemia
J. Immunol.,
October 15, 2004;
173(8):
5036 - 5045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. J. Aarts, O. Roovers, A. C. Ward, and I. P. Touw
Receptor activation and 2 distinct COOH-terminal motifs control G-CSF receptor distribution and internalization kinetics
Blood,
January 15, 2004;
103(2):
571 - 579.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Lehman, V. Calvo, and J. Gomez-Cambronero
Mechanism of Ribosomal p70S6 Kinase Activation by Granulocyte Macrophage Colony-stimulating Factor in Neutrophils: COOPERATION OF A MEK-RELATED, THR421/SER424 KINASE AND A RAPAMYCIN-SENSITIVE, mTOR-RELATED THR389 KINASE
J. Biol. Chem.,
July 18, 2003;
278(30):
28130 - 28138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-Q. Ning, J. Li, and R. J. Arceci
Signal transducer and activator of transcription 3 activation is required for Asp816 mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells
Blood,
June 1, 2001;
97(11):
3559 - 3567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
