Endothelial precursors and mature endothelial cells are increased in the peripheral blood of myelodysplastic syndromes

Abstract

Increased angiogenesis has been demonstrated to be a significant prognostic factor in many solid tumors. In the oncohematological setting, it has been associated with myelodysplastic syndromes (MDS), chronic myeloid leukemia, acute lymphoid, and myeloid leukemias. Recently, increased circulating endothelial cells (CECs) have been associated with breast cancer and non-Hodgkin lymphoma (NHL). Based on these premises we analysed total and activated CECs, and endothelial precursors (CEPs) in 50 MDS patients and 20 healthy donors. CECs and CEPs were quantified by flow cytometry. CEC levels were compared with bone marrow (BM) microvessel density (MVD). In addition, some angiogenic factors, namely vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and soluble VEGF-Receptor2 (VEGFR2), were tested in the sera from 25 MDS patients. Total, activated CECs and CEPs were significantly increased in MDS when compared to control group (p<0.0001); whereas in the MDS cases no association was found with French--American--British (FAB), International Prognostic Scoring System (IPSS) subtypes or survival. Patients with higher CECs also showed higher MVD. Among the cytokines analysed, sVEGFR2 was significantly higher in the lower IPSS risk classes, while the levels of bFGF directly correlated with total and activated CECs. Taken together these data strengthen the hypothesis of a possible role of angiogenesis in MDS pathogenesis.

Vascular Endothelial Growth Factor–Mediated Decrease in Plasma Soluble Vascular Endothelial Growth Factor Receptor-2 Levels as a Surrogate Biomarker for Tumor Growth

“…www.aacrjournals.org in a variety of cancers, including breast and colorectal carcinomas (35), melanoma (20), and a number of blood cell-related malignancies (21)(22)(23)(24); however, the utility of this protein as a potential biomarker remains unclear. To further investigate the relationship between sVEGFR-2 levels and tumor burden, we examined plasma obtained from various preclinical mouse tumor models that included spontaneous and implanted tumors, as well as localized and metastatic disease.…”

“…We first reported the existence of this 160-kDa truncated protein, which could be detected in both mouse and human plasma (19). Recent clinical studies have involved investigations into its potential as a surrogate biomarker for tumor progression or survival in melanoma (20), myelodysplastic syndromes (21), as well as in various leukemias (22)(23)(24). However, no clear pattern has yet emerged to indicate the utility of monitoring circulating sVEGFR-2 in the clinical setting, how it relates to tumor growth, and the underlying mechanisms governing observed changes.…”

Progenitor Marker CD133 mRNA Is Elevated in Peripheral Blood of Cancer Patients with Bone Metastases

“…The clinical relevance of increased endothelial progenitor cells in human tumor angiogenesis is, however, still controversial. First, there are no reports of increased endothelial progenitor cells in the peripheral blood of patients with solid tumors, although an increase has been reported in patients with myelodysplastic disorders (23), multiple myeloma (24), and infantile hemangioma (25). Second, increased endothelial progenitor cells have not been implicated as a predictor of poor prognosis in patients with cancer.…”

Immunophenotypic, cytogenetic and functional characterization of circulating endothelial cells in myelodysplastic syndromes

“…13 In addition, increased bone marrow angiogenesis may participate in the pathophysiology of these disorders. 14,15 Preliminary data indicate that endothelial cells are increased in the peripheral blood (PB) of MDS patients, 16 but their biological characteristics and their possible relationship with the malignant clone remain to be clarified.…”