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