Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
Blood, 1 September 2006, Vol. 108, No. 5, pp. 1652-1660.
Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2006-02-002030.


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2006-02-002030v1
108/5/1652    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lacout, C.
Right arrow Articles by Villeval, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lacout, C.
Right arrow Articles by Villeval, J.-L.
Related Collections
Right arrow Hematopoiesis and Stem Cells
Right arrow Neoplasia
Right arrow Oncogenes and Tumor Suppressors
Right arrowRelated Articles in Blood Online
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

NEOPLASIA

JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis

Catherine Lacout, Didier F. Pisani, Micheline Tulliez, Françoise Moreau Gachelin, William Vainchenker, and Jean-Luc Villeval

From the Institut National de la Sante et de la Recherche Medicale (INSERM) U790, Université Paris XI, Institut Gustave Roussy (IGR), Villejuif, France; Hôpital Cochin, Université Paris V, Paris, France; and INSERM U528, Institut Curie, Université Paris V, Paris, France.

A JAK2V617F mutation is frequently found in several BCR/ABL-negative myeloproliferative disorders. To address the contribution of this mutant to the pathogenesis of these different myeloproliferative disorders, we used an adoptive transfer of marrow cells transduced with a retrovirus expressing JAK2V617F in recipient irradiated mice. Hosts were analyzed during the 6 months after transplantation. For a period of 3 months, mice developed polycythemia, macrocytosis and usually peripheral blood granulocytosis. Transient thrombocytosis was only observed in a low-expresser group. All mice displayed trilineage hyperplasia in marrow and spleen along with an amplification of myeloid and erythroid progenitor cells and a formation of endogenous erythroid colonies. After 3 to 4 months, polycythemia regressed, abnormally shaped red blood cells and platelets were seen in circulation, and a deposition of reticulin fibers was observed in marrow and spleen. Development of fibrosis was associated with anemia, thrombocytopenia, high neutrophilia, and massive splenomegaly. These features mimic human polycythemia vera and its evolution toward myelofibrosis. This work demonstrates that JAK2V617F is sufficient for polycythemia and fibrosis development and offers an in vivo model to assess novel therapeutic approaches for JAK2V617F-positive pathologies. Questions remain regarding the exact contribution of JAK2V617F in other myeloproliferative disorders.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Articles in Blood Online:

JAK2V617F: prevalence in a large Chinese hospital population
Xuesong Xu, Qi Zhang, Jian Luo, Shu Xing, Qingshan Li, Sanford B. Krantz, Xueqi Fu, and Zhizhuang Joe Zhao
Blood 2007 109: 339-342. [Abstract] [Full Text] [PDF]

Animal models of the MPD: lack of the clones
Jerry L. Spivak
Blood 2006 108: 1427-1428. [Full Text] [PDF]



This article has been cited by other articles:


Home page
BloodHome page
I. Plo, M. Nakatake, L. Malivert, J.-P. de Villartay, S. Giraudier, J.-L. Villeval, L. Wiesmuller, and W. Vainchenker
JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders
Blood, August 15, 2008; 112(4): 1402 - 1412.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. L. Spivak and R. T. Silver
The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal
Blood, July 15, 2008; 112(2): 231 - 239.
[Full Text] [PDF]


Home page
BloodHome page
E. O. Hexner, C. Serdikoff, M. Jan, C. R. Swider, C. Robinson, S. Yang, T. Angeles, S. G. Emerson, M. Carroll, B. Ruggeri, et al.
Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders
Blood, June 15, 2008; 111(12): 5663 - 5671.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Xing, T. H. Wanting, W. Zhao, J. Ma, S. Wang, X. Xu, Q. Li, X. Fu, M. Xu, and Z. J. Zhao
Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice
Blood, May 15, 2008; 111(10): 5109 - 5117.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
A. Dusa, J. Staerk, J. Elliott, C. Pecquet, H. A. Poirel, J. A. Johnston, and S. N. Constantinescu
Substitution of Pseudokinase Domain Residue Val-617 by Large Non-polar Amino Acids Causes Activation of JAK2
J. Biol. Chem., May 9, 2008; 283(19): 12941 - 12948.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
R. Tiedt, H. Hao-Shen, M. A. Sobas, R. Looser, S. Dirnhofer, J. Schwaller, and R. C. Skoda
Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice
Blood, April 15, 2008; 111(8): 3931 - 3940.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. S. Wilkins, W. N. Erber, D. Bareford, G. Buck, K. Wheatley, C. L. East, B. Paul, C. N. Harrison, A. R. Green, and P. J. Campbell
Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes
Blood, January 1, 2008; 111(1): 60 - 70.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
G. Barosi, G. Bergamaschi, M. Marchetti, A. M. Vannucchi, P. Guglielmelli, E. Antonioli, M. Massa, V. Rosti, R. Campanelli, L. Villani, et al.
JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis
Blood, December 1, 2007; 110(12): 4030 - 4036.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. V. Lopes, J. M. Pacheco, and D. Dingli
Acquired hematopoietic stem-cell disorders and mammalian size
Blood, December 1, 2007; 110(12): 4120 - 4122.
[Abstract] [Full Text] [PDF]


Home page
Stem CellsHome page
A. Pardanani, T. L. Lasho, C. Finke, R. A. Mesa, W. J. Hogan, R. P. Ketterling, D. G. Gilliland, and A. Tefferi
Extending Jak2V617F and MplW515 Mutation Analysis to Single Hematopoietic Colonies and B and T Lymphocytes
Stem Cells, September 1, 2007; 25(9): 2358 - 2362.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. M. Vannucchi, E. Antonioli, P. Guglielmelli, A. Rambaldi, G. Barosi, R. Marchioli, R. M. Marfisi, G. Finazzi, V. Guerini, F. Fabris, et al.
Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia
Blood, August 1, 2007; 110(3): 840 - 846.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Dupont, A. Masse, C. James, I. Teyssandier, Y. Lecluse, F. Larbret, V. Ugo, P. Saulnier, S. Koscielny, J. P. Le Couedic, et al.
The JAK2 617V>F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera
Blood, August 1, 2007; 110(3): 1013 - 1021.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
O. Wagner-Ballon, D. F. Pisani, T. Gastinne, M. Tulliez, R. Chaligne, C. Lacout, F. Aurade, J.-L. Villeval, P. Gonin, W. Vainchenker, et al.
Proteasome inhibitor bortezomib impairs both myelofibrosis and osteosclerosis induced by high thrombopoietin levels in mice
Blood, July 1, 2007; 110(1): 345 - 353.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
A. Tefferi
Primary myelofibrosis and its paraneoplastic stromal effects
Haematologica, May 1, 2007; 92(5): 577 - 579.
[Full Text] [PDF]


Home page
BloodHome page
S. Malinge, R. Ben-Abdelali, C. Settegrana, I. Radford-Weiss, M. Debre, K. Beldjord, E. A. Macintyre, J.-L. Villeval, W. Vainchenker, R. Berger, et al.
Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia
Blood, March 1, 2007; 109(5): 2202 - 2204.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
Z. Li, M. Xu, S. Xing, W. T. Ho, T. Ishii, Q. Li, X. Fu, and Z. J. Zhao
Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell Growth
J. Biol. Chem., February 9, 2007; 282(6): 3428 - 3432.
[Abstract] [Full Text] [PDF]


Home page
NEJMHome page
L. M. Scott, W. Tong, R. L. Levine, M. A. Scott, P. A. Beer, M. R. Stratton, P. A. Futreal, W. N. Erber, M. F. McMullin, C. N. Harrison, et al.
JAK2 Exon 12 Mutations in Polycythemia Vera and Idiopathic Erythrocytosis
N. Engl. J. Med., February 1, 2007; 356(5): 459 - 468.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
R. Skoda
The Genetic Basis of Myeloproliferative Disorders
Hematology, January 1, 2007; 2007(1): 1 - 10.
[Abstract] [Full Text] [PDF]


Home page
Stem CellsHome page
P. Guglielmelli, R. Zini, C. Bogani, S. Salati, A. Pancrazzi, E. Bianchi, F. Mannelli, S. Ferrari, M.-C. Le Bousse-Kerdiles, A. Bosi, et al.
Molecular Profiling of CD34+ Cells in Idiopathic Myelofibrosis Identifies a Set of Disease-Associated Genes and Reveals the Clinical Significance of Wilms' Tumor Gene 1 (WT1)
Stem Cells, January 1, 2007; 25(1): 165 - 173.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
X. Xu, Q. Zhang, J. Luo, S. Xing, Q. Li, S. B. Krantz, X. Fu, and Z. J. Zhao
JAK2V617F: prevalence in a large Chinese hospital population
Blood, January 1, 2007; 109(1): 339 - 342.
[Abstract] [Full Text] [PDF]


Home page
NEJMHome page
P. J. Campbell and A. R. Green
The Myeloproliferative Disorders
N. Engl. J. Med., December 7, 2006; 355(23): 2452 - 2466.
[Full Text] [PDF]


Home page
Cancer Res.Home page
T. G.P. Bumm, C. Elsea, A. S. Corbin, M. Loriaux, D. Sherbenou, L. Wood, J. Deininger, R. T. Silver, B. J. Druker, and M. W.N. Deininger
Characterization of Murine JAK2V617F-Positive Myeloproliferative Disease
Cancer Res., December 1, 2006; 66(23): 11156 - 11165.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. A. Kennedy, F. Barabe, B. J. Patterson, J. Bayani, J. A. Squire, D. L. Barber, and J. E. Dick
Expression of TEL-JAK2 in primary human hematopoietic cells drives erythropoietin-independent erythropoiesis and induces myelofibrosis in vivo
PNAS, November 7, 2006; 103(45): 16930 - 16935.
[Abstract] [Full Text] [PDF]


Home page
ASH Education BookHome page
R. L. Levine and G. Wernig
Role of JAK-STAT Signaling in the Pathogenesis of Myeloproliferative Disorders
Hematology, January 1, 2006; 2006(1): 233 - 239.
[Abstract] [Full Text] [PDF]



 click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020