Dominant contribution of malignant endothelial cells to endotheliopoiesis in chronic myeloid leukemia.
ABSTRACT Although it has been well-established that hemangioblasts are present in chronic myeloid leukemia (CML) and contribute to both malignant hematopoiesis and endotheliopoiesis, the real contribution of CML-derived endothelial cells to endotheliopoiesis in CML patients has never been evaluated. The current study sought to determine CML-derived endotheliopoiesis in patients with CML.
Endothelial cells were isolated from the bone marrow or peripheral blood of six newly diagnosed CML patients using an immunomagnetic approach. The resulting endothelial cells were immediately subjected to fluorescence in situ hybridization analysis to determine BCR-ABL-positive endothelial cells.
The purity of isolated endothelial cells was 94.47% +/- 2.37%. In bone marrow, the BCR-ABL-positive endothelial cells accounted for 70.8% +/- 10.7% of total freshly isolated endothelial cells. In peripheral blood, however, the BCR-ABL-positive endothelial cells accounted for only 20.8% +/- 9.8% of isolated endothelial cells.
The present data demonstrate a dominant contribution of CML-derived endothelial cells to endotheliopoiesis in newly diagnosed CML, and provide the rationale for targeting hemangioblasts and angiogenesis in management of CML.
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ABSTRACT: In multiple myeloma (MM), circulating endothelial cells (CECs) represent a vascular marker of angiogenesis and may reflect tumor mass. In this report, we showed that, in 5 MM patients with 13q14 deletion, CECs carried the same chromosome aberration as the neoplastic plasma cells (11%-32% of CECs with 13q14 deletion). Most of the CECs displayed immunophenotypic features of endothelial progenitor cells as they expressed CD133, a marker gradually lost during endothelial differentiation and absent on mature endothelial cells. To the contrary, in 3 patients with monoclonal gammopathy of undetermined significance and 13q14 deletion, CECs were cytogenetically normal and had a mature immunophenotype. In MM CECs, immunoglobulin genes were clonally rearranged. These findings suggest a possible origin of CECs from a common hemangioblast precursor that can give rise to both plasma cells and endothelial cells and point to a direct contribution of MM-derived CECs to tumor vasculogenesis and possibly to the spreading and progression of the disease.Blood 04/2006; 107(6):2531-5. · 9.06 Impact Factor
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ABSTRACT: Circulating endothelial cells (CECs) are associated with neoangiogenesis in various malignant disorders. Using flow cytometry, we studied CECs in 128 patients with myelodysplastic syndrome (MDS). MDS patients had higher CEC levels than controls (P<0.001), and an inverse relationship was found between CECs and international prognostic scoring system risk (r=-0.55, P<0.001). There was a positive correlation between marrow microvessel density and CECs, low-risk patients showing the strongest association (r=0.62, P<0.001). We calculated a progenitor-to-mature CEC ratio, which was higher in MDS patients than in healthy subjects (P<0.001), the highest values were found at diagnosis. CECs assessed by flow cytometry positively correlated with the ability to produce endothelial colony-forming cells in vitro (ECFCs; r=0.57, P=0.021), which was significantly higher in MDS patients than in controls (P=0.011). Fluorescence in situ hybridization analysis showed that a variable proportion of CECs (from 40 to 84%) carried the same chromosomal aberration as the neoplastic clone, while endothelial cells isolated from in vitro assays were negative. This study suggests that CECs reflect the abnormal angiogenesis found in MDS, especially in the early stages of the disease. The increased number of functional endothelial progenitor cells in MDS strengthens the rationale for therapeutic interventions aimed at restoring a normal interaction between hematopoietic progenitors and marrow microenvironment.Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2008; 22(3):530-7. · 10.16 Impact Factor
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ABSTRACT: The existence of adult haemangioblasts with dual haematopoietic and endothelial developmental potential was confirmed after detection of Ph(+) vascular endothelial cells in chronic myeloid leukaemia (CML) patients. Blood outgrowth endothelial cells (OECs) from CML patients were found not to harbour the Philadelphia translocation and were thus not clonally related to BRC/ABL1(+) hematopoietic progenitors, but comprised a distinct subfraction of endothelial cells. Remarkably, the frequency of CML-derived OECs was 9-fold higher as compared to healthy donors (n = 19 and n = 300, respectively; P < 0.0001) and these cells showed increased proliferative potential, possibly reflecting the mobilisation of OEC progenitors by pro-angiogenic cytokines.British Journal of Haematology 07/2008; 142(1):115-8. · 4.94 Impact Factor