|
|
Blood, 1 December 2004, Vol. 104, No. 12, pp. 3573-3580.
Prepublished online as a Blood First Edition Paper on August 3, 2004; DOI 10.1182/blood-2004-01-0193.
 Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1low mice
Lucia Centurione,
Angela Di Baldassarre,
Maria Zingariello,
Domenico Bosco,
Valentina Gatta,
Rosa Alba Rana,
Vincenzo Langella,
Antonio Di Virgilio,
Alessandro M. Vannucchi, and
Anna Rita Migliaccio
From the Departments of Biomorphology and Biomedical Sciences, University "G. D'Annunzio," Chieti, Italy; CNR Institute for Organ Transplantation and Immunocytology, Chieti, Italy; Experimental Zoo-prophylactic Institute "G. Caporale," Teramo, Italy; Department of Hematology University of Firenze, Florence, Italy; and Laboratories of Security and Quality of Animal Experimentation and of Clinical Biochemistry, Istituto Superiore Sanità, Rome, Italy.
Deletion of megakaryocytic-specific regulatory sequences of GATA-1 (Gata1tm2Sho or GATA-1low mutation) results in severe thrombocytopenia, because of defective thrombocytopoiesis, and myelofibrosis. As documented here, the GATA-1low mutation blocks megakaryocytic maturation between stage I and II, resulting in accumulation of defective megakaryocytes (MKs) in the tissues of GATA-1low mice. The block in maturation includes failure to properly organize  granules because von Willebrand factor is barely detectable in mutant MKs, and P-selectin, although normally expressed, is found frequently associated with the demarcation membrane system (DMS) instead of within granules. Conversely, both von Willebrand factor and P-selectin are barely detectable in GATA-1low platelets. Mutant MKs are surrounded by numerous myeloperoxidase-positive neutrophils, some of which appear in the process to establish contact with MKs by fusing their membrane with those of the DMS. As a result, 16% (in spleen) to 34% (in marrow) of GATA-1low MKs contain 1 to 3 neutrophils embedded in a vacuolated cytoplasm. The neutrophil-embedded GATA-1low MKs have morphologic features (high electron density and negativity to TUNEL staining) compatible with those of cells dying from para-apoptosis. We suggest that such an increased and pathologic neutrophil emperipolesis may represent one of the mechanisms leading to myelofibrosis by releasing fibrogenic MK cytokines and neutrophil proteases in the microenvironment.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Pieri, C. Bogani, P. Guglielmelli, M. Zingariello, R. A. Rana, N. Bartalucci, A. Bosi, and A. M. Vannucchi
The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera
Haematologica,
November 1, 2009;
94(11):
1537 - 1545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Migliaccio, F. Martelli, M. Verrucci, M. Sanchez, M. Valeri, G. Migliaccio, A. M. Vannucchi, M. Zingariello, A. Di Baldassarre, B. Ghinassi, et al.
Gata1 expression driven by the alternative HS2 enhancer in the spleen rescues the hematopoietic failure induced by the hypomorphic Gata1low mutation
Blood,
September 3, 2009;
114(10):
2107 - 2120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. E. Elagib, I. S. Mihaylov, L. L. Delehanty, G. C. Bullock, K. D. Ouma, J. F. Caronia, S. L. Gonias, and A. N. Goldfarb
Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation
Blood,
December 15, 2008;
112(13):
4884 - 4894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zingariello, D. Bosco, B. Ghinassi, R. A. Rana, F. A. Manzoli, and A. R. Migliaccio
Peripolesis of Fibroblasts around Megakaryocytes: A New Pathological Cellular Interaction Leading to Megakaryocyte Para-Apoptosis in Gata1low Mice.
Blood (ASH Annual Meeting Abstracts),
November 16, 2006;
108(11):
3592 - 3592.
[Abstract]
[PDF]
|
|
|
|
|
|
|
F. Martelli, B. Ghinassi, B. Panetta, E. Alfani, V. Gatta, A. Pancrazzi, C. Bogani, A. M. Vannucchi, F. Paoletti, G. Migliaccio, et al.
Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds
Blood,
December 15, 2005;
106(13):
4102 - 4113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi
Pathogenesis of Myelofibrosis With Myeloid Metaplasia
J. Clin. Oncol.,
November 20, 2005;
23(33):
8520 - 8530.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zingariello, B. Ghinassi, R. A. Rana, L. R.N. Lorenzini, A. M. Vannucchi, F. Paoletti, and A. R. F. Migliaccio
The Ultrastructure Features of the Advanced Stages of Fibrosis in GATA-1low Mice Are Similar to Those Found in Wound Healing.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
3514 - 3514.
[Abstract]
|
|
|
|
|
|
|
A. M. Vannucchi, A. Pancrazzi, P. Guglielmelli, S. Di Lollo, C. Bogani, G. Baroni, L. Bianchi, A. R. Migliaccio, A. Bosi, and F. Paoletti
Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic Myelofibrosis
Am. J. Pathol.,
September 1, 2005;
167(3):
849 - 858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Xu, E. Bruno, J. Chao, S. Huang, G. Finazzi, S. M. Fruchtman, U. Popat, J. T. Prchal, G. Barosi, R. Hoffman, et al.
Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases
Blood,
June 1, 2005;
105(11):
4508 - 4515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Vannucchi, L. Bianchi, F. Paoletti, A. Pancrazzi, E. Torre, M. Nishikawa, M. Zingariello, A. Di Baldassarre, R. A. Rana, R. Lorenzini, et al.
A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-{beta}1 in the development of myelofibrosis
Blood,
May 1, 2005;
105(9):
3493 - 3501.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
