Evaluation of circulating endothelial cells as noninvasive marker of angiogenesis in patients with chronic lymphocytic leukemia

Abstract

An increased angiogenesis has been documented in bone marrow and lymph nodes of patients with chronic lymphocytic leukemia (CLL). There is accumulating evidence that circulating endothelial cells (CECs) play an important role in angiogenesis. The aim of our study was to compare the number of CECs in peripheral blood of CLL patients and healthy donors and to correlate these numbers with bone marrow microvessel density (MVD) and known prognostic factors in CLL. Proportions of resting CECs (rCECs), activated CECs (aCECs), apoptotic CECs (apoCECs) and circulating precursor endothelial cells (CPECs) were estimated by flow cytometry in 104 untreated CLL patients and 29 healthy blood donors. The MVD was analysed in the bone marrow biopsy in 21 CLL patients and 11 controls using the ‘hot spot analysis’ of vessels' density (×200 HPS). We found significantly higher numbers of CPECs, rCECs, aCECs and apoCECs in CLL patients than in healthy controls (p < 0.001 for all comparisons). Furthermore, the rCECs number was higher in advanced versus low clinical stage CLL (median 17.5 cells/µL vs. 13.5 cells/µL, p = 0.05). The MVD was significantly higher in the bone marrow of CLL patients when compared with controls (p = 0.016). However, we did not find any correlation between MVD and different CECs populations. In conclusion, the number of CECs is increased in CLL and correlates with stage of the disease, but does not seem to directly reflect the intensity of neovascularisaton in the bone marrow.