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

Abstract

(2013) ANGPT2 promoter methylation is strongly associated with gene expression and prognosis in chronic lymphocytic leukemia, Epigenetics, 8:7,[720][721][722][723][724][725][726][727][728][729]

The progress of angiogenic factors in the development of leukemias

“…CLL patients may have a negative impact on their disease course with a notable increase of Ang-2 ligand expression (97), which is accompanied with an aberrant vascularization in (bone marrow) BM sections (98). Recent epigenetic evidence showed that Ang-2 displays lower DNA methylation in CLL and correlates with poor prognosis and shorter survival (97). Additionally, Binet staging can be linked to elevated levels of Ang-2 (93).…”

Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro

“…Since CLL patients display lower Ang1 level, we could infer that accessory cells in the CLL microenvironment, which normally secrete Ang1 and maintain quiescent Ang-Tie2 signalling, or CLL themselves, have lost their Ang1 secretion ability. Since increased expression of Ang2 [28] is associated with changes in the Ang2 promoter methylation pattern [8], a similar scenario could explain the lower Ang1 levels detected in CLL samples. Further research is necessary to identify the specific cell populations with compromised Ang1-expressing capabilities in the CLL microenvironments.…”

“…Previously Kay et al analysed the expression of some angiogenic factors and receptors in CLL patients, detecting expression of Tie1 and Ang1 and similarly failed to detect Tie2 transcripts [2]. Ang2 expression in CLL and its correlation with disease progression has been extensively described in the literature [6,8,28]. Furthermore, Aguayo et al described Tie1 expression [29] in CLL samples and its correlation with CLL disease stage.…”

“…CLL researchers report a concomitant overexpression of Ang2 and pro-angiogenic VEGF in CLL patients [7]. Ang2 negatively impacts the CLL disease course [8] correlating not only with Binet staging, but also with high β-2-microglobulin levels, unmutated IgV H , elevated CD38-ZAP70 status, and intermediate-to-high risk cytogenetic profiles [6]. What is more, Ang2 levels also correlate with shorter time to first treatment (TTFT), disease aggressiveness, and rapid disease progression [36].…”

“…Researchers also detected high levels of vascular endothelial growth factor (VEGF) in CLL patients [2] and together with bFGF, VEGF is one of the most studied angiogenic factors in cancer research. Similar to the overexpression of VEGF and bFGF, recent research describing the overexpression of angiopoietin-2 (Ang2) in CLL cases highlights the relevance of angiopoietins in the CLL microenvironment [6][7][8]. There is a correlation between high plasma levels of Ang2 with disease progression, and in addition, isolated CLL cells abundantly secrete Ang2 in culture.…”