|
|
 Previous Article | Table of Contents | Next Article 
Multiple Inhibitory Cytokines Induce Deregulated Progenitor
Growth and Apoptosis in Hematopoietic Cells From
Fac / Mice
Laura S. Haneline,
Hal E. Broxmeyer,
Scott Cooper,
Giao Hangoc,
Madeleine Carreau,
Manuel Buchwald, and
D. Wade Clapp
From the Department of Pediatrics, Herman B Wells Center for
Pediatric Research, Indiana University School of Medicine; the
Department of Microbiology/Immunology, Indiana University School of
Medicine; Walther Oncology Center, Indiana University School of
Medicine, Indianapolis; Walther Cancer Institute, Indianapolis, IN; the
Department of Genetics, Hospital for Sick Children, Toronto, Ontario,
Canada; and the Department of Molecular and Medical Genetics,
University of Toronto, Toronto, Ontario, Canada.
We used a murine model containing a disruption of the murine
homologue (Fac) of Fanconi Anemia group C (FAC)
to evaluate the role of Fac in the pathogenesis of bone marrow
(BM) failure. Methylcellulose cultures of BM cells from
Fac / and Fac+/+ mice
were established to examine the growth of multipotent and lineage-restricted progenitors containing inhibitory cytokines, including interferon- (IFN-), tumor necrosis factor-
(TNF-), and macrophage inflammatory protein-1 (MIP-1).
Clonogenic growth of Fac/ progenitors was
reduced by 50% at 50- to 100-fold lower concentrations of all
inhibitory cytokines evaluated. We hypothesized that the aberrant
responsiveness to inhibitory cytokines in clonogenic cells may be a
result of deregulated apoptosis. To test this hypothesis, we performed
the TUNEL assay on purified populations of primary BM cells enriched
for hematopoietic progenitors or differentiated myeloid cells. After
stimulation with TNF-, accentuated apoptosis was observed in both
populations of Fac/ cells. In addition,
deregulated apoptosis was also noted in the most immature phenotypic
population of hematopoietic cells after stimulation with
MIP-1.Together these data suggest a role of Fac in affecting
the signaling of multiple cytokine pathways and support
cytokine-mediated apoptosis as a major mechanism responsible for BM
failure observed in FA patients.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4092-4098
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Briot, G. Mace-Aime, F. Subra, and F. Rosselli
Aberrant activation of stress-response pathways leads to TNF-{alpha} oversecretion in Fanconi anemia
Blood,
February 15, 2008;
111(4):
1913 - 1923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Broxmeyer, S. Sehra, S. Cooper, L. M. Toney, S. Kusam, J. J. Aloor, C. C. Marchal, M. C. Dinauer, and A. L. Dent
Aberrant Regulation of Hematopoiesis by T Cells in BAZF-Deficient Mice
Mol. Cell. Biol.,
August 1, 2007;
27(15):
5275 - 5285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhang, D. P. Sejas, Y. Qiu, D. A. Williams, and Q. Pang
Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence
J. Cell Sci.,
May 1, 2007;
120(9):
1572 - 1583.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Sejas, R. Rani, Y. Qiu, X. Zhang, S. R. Fagerlie, H. Nakano, D. A. Williams, and Q. Pang
Inflammatory Reactive Oxygen Species-Mediated Hemopoietic Suppression in Fancc-Deficient Mice
J. Immunol.,
April 15, 2007;
178(8):
5277 - 5287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Gilner, W. G. Walton, K. Gush, and S. L. Kirby
Antibodies to Stem Cell Marker Antigens Reduce Engraftment of Hematopoietic Stem Cells
Stem Cells,
February 1, 2007;
25(2):
279 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. C. Bagby and G. Meyers
Bone Marrow Failure as a Risk Factor for Clonal Evolution: Prospects for Leukemia Prevention
Hematology,
January 1, 2007;
2007(1):
40 - 46.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Si, S. Ciccone, F.-C. Yang, J. Yuan, D. Zeng, S. Chen, H. J. van de Vrugt, J. Critser, F. Arwert, L. S. Haneline, et al.
Continuous in vivo infusion of interferon-gamma (IFN-{gamma}) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice
Blood,
December 15, 2006;
108(13):
4283 - 4287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Liu and S. R. Ellis
Ribosomes and marrow failure: coincidental association or molecular paradigm?
Blood,
June 15, 2006;
107(12):
4583 - 4588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Bijangi-Vishehsaraei, M. R. Saadatzadeh, A. Werne, K. A. W. McKenzie, R. Kapur, H. Ichijo, and L. S. Haneline
Enhanced TNF-{alpha}-induced apoptosis in Fanconi anemia type C-deficient cells is dependent on apoptosis signal-regulating kinase 1
Blood,
December 15, 2005;
106(13):
4124 - 4130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Habi, M.-C. Delisle, N. Messier, and M. Carreau
Lack of Self-Renewal Capacity in Fancc-/- Stem Cells After Ex Vivo Expansion
Stem Cells,
September 1, 2005;
23(8):
1135 - 1141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhang, J. Li, D. P. Sejas, and Q. Pang
Hypoxia-reoxygenation induces premature senescence in FA bone marrow hematopoietic cells
Blood,
July 1, 2005;
106(1):
75 - 85.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Li, M. M. Le Beau, S. Ciccone, F.-C. Yang, B. Freie, S. Chen, J. Yuan, P. Hong, A. Orazi, L. S. Haneline, et al.
Ex vivo culture of Fancc-/- stem/progenitor cells predisposes cells to undergo apoptosis, and surviving stem/progenitor cells display cytogenetic abnormalities and an increased risk of malignancy
Blood,
May 1, 2005;
105(9):
3465 - 3471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Broxmeyer, C. M. Orschell, D. W. Clapp, G. Hangoc, S. Cooper, P. A. Plett, W. C. Liles, X. Li, B. Graham-Evans, T. B. Campbell, et al.
Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist
J. Exp. Med.,
April 18, 2005;
201(8):
1307 - 1318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mi and G. M. Kupfer
The Fanconi anemia core complex associates with chromatin during S phase
Blood,
January 15, 2005;
105(2):
759 - 766.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W. Freie, S. L. M. Ciccone, X. Li, P. A. Plett, C. M. Orschell, E. F. Srour, H. Hanenberg, D. Schindler, S.-H. Lee, and D. W. Clapp
A Role for the Fanconi Anemia C Protein in Maintaining the DNA Damage-induced G2 Checkpoint
J. Biol. Chem.,
December 3, 2004;
279(49):
50986 - 50993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Qiao, J. Mi, J. B. Wilson, G. Zhi, N. R. Bucheimer, N. J. Jones, and G. M. Kupfer
Phosphorylation of Fanconi Anemia (FA) Complementation Group G Protein, FANCG, at Serine 7 Is Important for Function of the FA Pathway
J. Biol. Chem.,
October 29, 2004;
279(44):
46035 - 46045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhang, J. Li, D. P. Sejas, K. R. Rathbun, G. C. Bagby, and Q. Pang
The Fanconi Anemia Proteins Functionally Interact with the Protein Kinase Regulated by RNA (PKR)
J. Biol. Chem.,
October 15, 2004;
279(42):
43910 - 43919.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Li, Y. Yang, J. Yuan, P. Hong, B. Freie, A. Orazi, L. S. Haneline, and D. W. Clapp
Continuous in vivo infusion of interferon-gamma (IFN-{gamma}) preferentially reduces myeloid progenitor numbers and enhances engraftment of syngeneic wild-type cells in Fancc-/- mice
Blood,
August 15, 2004;
104(4):
1204 - 1209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Thomashevski, A. A. High, M. Drozd, J. Shabanowitz, D. F. Hunt, P. A. Grant, and G. M. Kupfer
The Fanconi Anemia Core Complex Forms Four Complexes of Different Sizes in Different Subcellular Compartments
J. Biol. Chem.,
June 18, 2004;
279(25):
26201 - 26209.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Saadatzadeh, K. Bijangi-Vishehsaraei, P. Hong, H. Bergmann, and L. S. Haneline
Oxidant Hypersensitivity of Fanconi Anemia Type C-deficient Cells Is Dependent on a Redox-regulated Apoptotic Pathway
J. Biol. Chem.,
April 16, 2004;
279(16):
16805 - 16812.
[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]
|
|
|
|
|
|
|
I. Brodeur, I. Goulet, C. S. Tremblay, C. Charbonneau, M.-C. Delisle, C. Godin, C. Huard, E. W. Khandjian, M. Buchwald, G. Levesque, et al.
Regulation of the Fanconi Anemia Group C Protein through Proteolytic Modification
J. Biol. Chem.,
February 6, 2004;
279(6):
4713 - 4720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Freie, X. Li, S. L. M. Ciccone, K. Nawa, S. Cooper, C. Vogelweid, L. Schantz, L. S. Haneline, A. Orazi, H. E. Broxmeyer, et al.
Fanconi anemia type C and p53 cooperate in apoptosis and tumorigenesis
Blood,
December 1, 2003;
102(12):
4146 - 4152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dufour, A. Corcione, J. Svahn, R. Haupt, V. Poggi, A. N. Beka'ssy, R. Scime, A. Pistorio, and V. Pistoia
TNF-{alpha} and IFN-{gamma} are overexpressed in the bone marrow of Fanconi anemia patients and TNF-{alpha} suppresses erythropoiesis in vitro
Blood,
September 15, 2003;
102(6):
2053 - 2059.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Li, P. A. Plett, Y. Yang, P. Hong, B. Freie, E. F. Srour, C. M. Orschell, D. W. Clapp, and L. S. Haneline
Fanconi anemia type C-deficient hematopoietic stem/progenitor cells exhibit aberrant cell cycle control
Blood,
September 15, 2003;
102(6):
2081 - 2084.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Matsumoto, K. E. Comatas, L. Liu, and J. S. Stamler
Screening for Nitric Oxide-Dependent Protein-Protein Interactions
Science,
August 1, 2003;
301(5633):
657 - 661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Lensch, M. Tischkowitz, T. A. Christianson, C. A. Reifsteck, S. A. Speckhart, P. M. Jakobs, M. E. O'Dwyer, S. B. Olson, M. M. Le Beau, S. V. Hodgson, et al.
Acquired FANCA dysfunction and cytogenetic instability in adult acute myelogenous leukemia
Blood,
July 1, 2003;
102(1):
7 - 16.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hadjur and F. R. Jirik
Increased sensitivity of Fancc-deficient hematopoietic cells to nitric oxide and evidence that this species mediates growth inhibition by cytokines
Blood,
May 15, 2003;
101(10):
3877 - 3884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Haneline, X. Li, S. L. M. Ciccone, P. Hong, Y. Yang, H. E. Broxmeyer, S.-H. Lee, A. Orazi, E. F. Srour, and D. W. Clapp
Retroviral-mediated expression of recombinant Fancc enhances the repopulating ability of Fancc-/- hematopoietic stem cells and decreases the risk of clonal evolution
Blood,
February 15, 2003;
101(4):
1299 - 1307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Pang, T. A. Christianson, W. Keeble, T. Koretsky, and G. C. Bagby
The Anti-apoptotic Function of Hsp70 in the Interferon-inducible Double-stranded RNA-dependent Protein Kinase-mediated Death Signaling Pathway Requires the Fanconi Anemia Protein, FANCC
J. Biol. Chem.,
December 13, 2002;
277(51):
49638 - 49643.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bogliolo, O. Cabre, E. Callen, V. Castillo, A. Creus, R. Marcos, and J. Surralles
The Fanconi anaemia genome stability and tumour suppressor network
Mutagenesis,
November 1, 2002;
17(6):
529 - 538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Aube, M. Lafrance, C. Charbonneau, I. Goulet, and M. Carreau
Hematopoietic Stem Cells from Fancc-/- Mice Have Lower Growth and Differentiation Potential in Response to Growth Factors
Stem Cells,
September 1, 2002;
20(5):
438 - 447.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Rio, J. C. Segovia, H. Hanenberg, J. A. Casado, J. Martinez, K. Gottsche, N. C. Cheng, H. J. Van de Vrugt, F. Arwert, H. Joenje, et al.
In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice
Blood,
August 28, 2002;
100(6):
2032 - 2039.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-S. Dai, N. Chevallier, S. Stone, M. C. Heinrich, M. McConnell, T. Reuter, H. E. Broxmeyer, J. D. Licht, L. Lu, and M. E. Hoatlin
The Effects of the Fanconi Anemia Zinc Finger (FAZF) on Cell Cycle, Apoptosis, and Proliferation Are Differentiation Stage-specific
J. Biol. Chem.,
July 12, 2002;
277(29):
26327 - 26334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yang, Y. Kuang, R. M. De Oca, T. Hays, L. Moreau, N. Lu, B. Seed, and A. D. D'Andrea
Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9
Blood,
December 1, 2001;
98(12):
3435 - 3440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Grompe and A. D'Andrea
Fanconi anemia and DNA repair
Hum. Mol. Genet.,
October 1, 2001;
10(20):
2253 - 2259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Pang, T. A. Christianson, W. Keeble, J. Diaz, G. R. Faulkner, C. Reifsteck, S. Olson, and G. C. Bagby
The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality
Blood,
September 1, 2001;
98(5):
1392 - 1401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hadjur, K. Ung, L. Wadsworth, J. Dimmick, E. Rajcan-Separovic, R. W. Scott, M. Buchwald, and F. R. Jirik
Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase
Blood,
August 15, 2001;
98(4):
1003 - 1011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Dror and M. H. Freedman
Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway
Blood,
May 15, 2001;
97(10):
3011 - 3016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Wajnrajch, J. M. Gertner, Z. Huma, J. Popovic, K. Lin, P. C. Verlander, S. D. Batish, P. F. Giampietro, J. G. Davis, M. I. New, et al.
Evaluation of Growth and Hormonal Status in Patients Referred to the International Fanconi Anemia Registry
Pediatrics,
April 1, 2001;
107(4):
744 - 754.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Pang, W. Keeble, J. Diaz, T. A. Christianson, S. Fagerlie, K. Rathbun, G. R. Faulkner, M. O'Dwyer, and G. C. Bagby Jr
Role of double-stranded RNA-dependent protein kinase in mediating hypersensitivity of Fanconi anemia complementation group C cells to interferon {gamma}, tumor necrosis factor-{alpha}, and double-stranded RNA
Blood,
March 15, 2001;
97(6):
1644 - 1652.
[Abstract]
[Full Text]
[PDF]
| |
