Haematologica, Vol 92, Issue 5, 597-604 doi:10.3324/haematol.11013
Copyright © 2007 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zetterberg, E.
Right arrow Articles by Palmblad, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zetterberg, E.
Right arrow Articles by Palmblad, J.
Related Collections
Right arrowRelated Article

Myeloproliferative Disorders

Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows

Eva Zetterberg, Alessandro M. Vannucchi, Anna Rita Migliaccio, William Vainchenker, Micheline Tulliez, Renée Dickie, Hans Hasselbalch, Rick Rogers, Jan Palmblad

From the Division of Hematology and Center for Inflammation and Hematology Research, Department of Medicine, The Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden (EZ, JP); Department of Hematology, University of Florence, Florence, Italy (AMV); Clinical Biochemistry, Istituto Superiore Sanità, Viale Regina Elena 299, 00161 Rome, Italy (ARM); IFR 54-INSERM U 362 Institut Gustave Roussy, Villejuif, France (WV); Service d’Anatomie Pathologique, Hôpital Cochin, Paris, France (MT); BioMedical Imaging Lab, Harvard School of Public Health, Boston, MA, USA (RD, RR); Department of Hematology, Odense University Hospital, University of Southern Denmark, 5000 Odense, Denmark (HH)

Correspondence: Jan Palmblad, MD, PhD, Department of Medicine M54, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. E-mail: jan.palmblad{at}ki.se

Background and Objectives: Myelofibrotic bone marrow displays abnormal angiogenesis but the pathogenic mechanisms of this are poorly understood. Since pericyte abnormalities are described on solid tumor vessels we studied whether vessel morphology and pericyte coverage in bone marrow samples from patients with myelofibrosis differed from that in samples from controls.

Design and Methods: We assessed the microvascular density (MVD), vessel morphology and pericyte coverage in bone marrows from 19 myelofibrosis patients and nine controls. We also studied the same parameters in two mouse models of myelofibrosis, with genetic alterations affecting megakaryocyte differentiation (i.e. one model with low GATA-1 expression and the other with over-expression of thrombopoietin).

Results: In myelofibrotic marrows, MVD was 3.8-fold greater than in controls (p<0.001) and vessels displayed 5.9-fold larger mean perimeters (p<0.001). MVD was 1.8-fold greater in JAK2 V617F-positive than in negative patients (p=0.026). Moreover, 92±11 % of vessels in patients with myelofibrosis were pericyte-coated but only 51±20 % of vessels in controls (p<0.001). In the two mouse models of myelofibrosis caused by targeting megakaryocytopoesis, wide, pericyte-coated and morphologically aberrant vessels were detected. MVD was significantly greater in bone marrow and spleen samples from animals with myelofibrosis than in wild-type mice.

Interpretation and Conclusions: We conclude that angiogenesis is similarly abnormal in human and murine myelofibrosis with intense pericyte coating, presumably related to abnormal megakaryocytopoiesis.

Key words: angiogenesis, microvascular density, SMA, myelofibrosis, pericytes.


Related Article

Primary myelofibrosis and its paraneoplastic stromal effects
Ayalew Tefferi
Haematologica 2007 92: 577-579. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 haematolHome page
E. Zetterberg, U. Popat, H. Hasselbalch, J. Prchal, and J. Palmblad
Angiogenesis in pulmonary hypertension with myelofibrosis
Haematologica, June 1, 2008; 93(6): 945 - 946.
[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]