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

ANGPT2promoter methylation is strongly associated with gene expression and prognosis in chronic lymphocytic leukemia

“…Higher levels of ANGPT2 expression were associated with poorprognostic factors and with shorter TTFT and OS. This is in agreement with previous studies on the prognostic impact of ANGPT2 in CLL, [5][6][7] supporting the idea that ANGPT2 plays an important role in determining disease aggressiveness. This overexpression leading to increased angiogenesis in CLL [8][9][10] further supports that interactions between leukemic cells and the microenvironment could represent good targets for therapeutic interventions.…”

“…4,29,30 In previous studies, we and others have shown that a more aggressive CLL phenotype is characterized by higher levels of ANGPT2, increased angiogenesis and poor prognosis. [5][6][7][8][9][10] Considering the variability in ANGPT2 levels among CLL patients we here investigated the potential relation between ANGPT2 expression and promoter DNA methylation in a wellcharacterized CLL cohort, in order to understand if epigenetic mechanisms are involved in ANGPT2 regulation.…”

“…[1][2][3][4] We and others have recently demonstrated that higher expression of angiopoietin-2 (ANGPT2) in CLL confers poor prognosis and that the ANGPT2 produced by leukemic cells is able to induce an increased angiogenesis, characteristic of CLL patients with an aggressive disease. [5][6][7][8][9][10] ANGPT2 is a secreted glycoprotein able to increase vessel plasticity, by binding to the Tie-2 receptor on endothelial cells and blocking ANGPT1 function. The vessel destabilization induced by ANGPT2 can lead to formation of new vessels or to regression of the existing vessels, depending on the presence or not of vascular endothelial factor (VEGF).…”

“…[26][27][28] Of particular interest was the finding of a higher ANGPT2 methylation in the IGHV-mutated subset suggesting a possible epigenetic regulation of this gene. 26,27 Since ANGPT2 expression has been demonstrated to vary considerably between these two subgroups of CLL patients, 5,6 ANGPT2 gene expression could be directly regulated by DNA methylation. To study this further, we assessed the methylation status of the ANGPT2 gene promoter as well as the ANGPT2 expression levels in a large, well-characterized CLL cohort.…”

Biological Prognostic Markers in Chronic Lymphocytic Leukemia

“…Its physiological role is the destruction of old blood vessels which is subsequently followed by neovascularization and blood vessel remodelling (59). Recently, Maffei et al have shown that circulating CLL cells are capable to produce an increased amount of Ang-2 (34). Results of our group (62) independently to results of others showed an increased expression of mRNA for angiopoietin in CLL patients with unmutated IgVH genes (36,54).…”