Journal
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
Volume 92, Issue 5, Pages 597-604Publisher
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.11013
Keywords
angiogenesis; microvascular density; SMA; myelofibrosis; pericytes
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Funding
- NIEHS NIH HHS [ES0002-39] Funding Source: Medline
- PHS HHS [HJ33009-16] Funding Source: Medline
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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). (VIVID 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.
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