Increased Angiogenesis in the Bone Marrow of Patients with Systemic Mastocytosis

Abstract

Recent data suggest that angiogenesis in the bone marrow (BM) is augmented and associated with growth of neoplastic cells in various hematological malignancies. Systemic mastocytosis (SM) is a neoplasm affecting multilineage and mast cell (MC)-committed hemopoietic progenitors. In the present study, we have assessed the BM microvessel density (MVD) by CD34 immunohistochemistry in 21 patients with SM, 5 with cutaneous mastocytosis (no BM infiltrates), and 5 control cases (normal BM). The median BM MVD was significantly higher in SM compared to cutaneous mastocytosis or controls (P < 0.05). In addition, a significant correlation (r ‫؍‬ 0.74) between the BM MVD and grade of MC infiltration (percent tryptase ؉ BM infiltrates) was found in SM. Moreover, the MVD was higher in MC infiltrates compared to the nonaffected adjacent marrow (P < 0.05). Immunohistochemical staining revealed expression of vascular endothelial growth factor in MC infiltrates. The notion that SM is associated with increased BM angiogenesis and vascular endothelial growth factor expression may have implications for the biology of disease and development of new treatment strategies.

Identification of Oncostatin M as a STAT5-Dependent Mediator of Bone Marrow Remodeling in KIT D816V-Positive Systemic Mastocytosis

“…These alterations include neoangiogenesis, thickened bone trabeculae, and sometimes massive bone marrow fibrosis. [3][4][5] In the present study, we show that HMC-1 cell-derived OSM stimulates in vitro growth of microvascular endothelial cells, osteoblasts, and fibroblasts. This finding indicates that neoplastic mast cells secrete sufficient amounts of active OSM to stimulate proliferation of mesenchymal cells.…”

“…Apart from mast cell infiltrates, alterations in the bone marrow microenvironment, including increased angiogenesis, thickened bone trabeculae, and sometimes bone marrow fibrosis, are found in these patients. [3][4][5] These bone marrow alterations are detectable independent of the category of mastocytosis, presence of eosinophilia, or the mast cell burden. It has also been shown that bone marrow stromal cells support growth and differentiation of mast cells.…”

The stromal composition of mast cell aggregates in systemic mastocytosis

“…In this regard, it was recently observed that antiangiogenic therapy in systemic mastocytosis did not result in the normalization of marrow findings including the amount of bone marrow fibrosis in treated patients, 36,37 or in significant clinical improvement. 37 Although an increase in bone marrow angiogenesis is reported in the majority of patients with systemic mastocytosis, 38,39 its pathogenesis is unclear and may not be directly linked to the mast cells themselves. 39 This conclusion is also supported by a recent study which has demonstrated the absence of direct correlation between microvessel density and the degree of bone marrow involvement by mast cell lesions or the expression of various angiogenic cytokines.…”

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

“…4 In addition to the well-established role of angiogenesis in solid tumors, 4 the increase in tumor vascularity has been previously investigated in a variety of hematological neoplasms, including acute lymphatic 15 and myeloid 16,17 leukemias, myelodysplastic syndromes, 14,18 Hodgkin's disease, 19 myeloma, 20-25 lymphoproliferative disorders, 26-31 systemic mastocytosis 32 and chronic myeloproliferative disorders, 5,14 including CIMF. 8 The number of small vessels in a tumor, or MVD, is considered a surrogate indicator of angiogenesis.…”