Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia

Abstract

Recent studies have shown that angiogenesis may be involved in the pathogenesis of hematopoietic malignancies, apart from its well-characterized role in the growth and metastasis of solid tumors. In this study, we quantified the degree of angiogenesis in B cell chronic lymphocytic leukemia (B-CLL) by measuring the microvessel density and hotspot density in bone marrow trephine biopsy sections with B-CLL involvement (n ‫؍‬ 12) and compared it to normal bone marrow sections (n ‫؍‬ 11). The B-CLL samples had a mean microvessel count/high power field (hpf) of 7.64 while the control samples had a mean microvessel count/hpf of 2.11 (P ‫؍‬ 0.0001). The mean hotspot density in the B-CLL sections (14.83/hotspot) was also significantly higher (P ‫؍‬ 0.0008) than the mean hotspot density in control bone marrow sections (7.09/hotspot). Both the microvessel density and hotspot density correlated positively with the clinical stage of the B-CLL patients. In a separate cohort of B-CLL patients, the median urine level of the angiogenic peptide, basic fibroblast growth factor (2216.5 pg/g, n ‫؍‬ 14), was significantly higher (P ‫؍‬ 0.0001) than the bFGF level in normal controls (1084 pg/g, n ‫؍‬ 58). These results indicate that angiogenesis may be involved in the pathogenesis of B-CLL.

Autocrine VEGF mediates the antiapoptotic effect of CD154 on CLL cells

“…Increased microvessel density has also been reported in the bone marrow of patients with CLL. 9 We suggested that increased angiogenesis might play an important role in the survival of tissue-phase CLL cells by providing metabolic support. 5 In addition to its role in angiogenesis, VEGF has been found to be an autocrine survival factor for some cell types including solid tumour and endothelial cells, [10][11][12] as well as CLL cells.…”

Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells

“…1 By measuring microvessel and hotspot densities in bone marrow trephine biopsies, Kini et al 2 showed that both parameters are higher in patients with B-cell lymphocytic leukemia (B-CLL) than in normal individuals, indicating that angiogenesis may be involved in the pathogenesis of this leukemia. Similar results were obtained by Wolowiec et al 3 who also found that B-CLL bone marrow displays a higher proliferative activity than normal bone marrow, as assessed by the mean number of nucleolar organizer regions.…”

Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status

“…1 Increased microvessel density in marrow Letters to the Editor and lymph node and increased levels of certain pro-angiogenetic factors in the blood and urine of CLL patients were observed. 2 Ang-2 has a pivotal role in the disruption of stability and quiescence of mature vasculature that coincides with the reinitiation of vascular remodelling and angiogenic sprouting in adult, as occurs in tumors. Abnormal serum levels of angiopoietin-2 (Ang-2) were found in several hematological malignancies.…”