Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia

作者：Maffei Rossana; Martinelli Silvia; Santachiara Rita; Rossi Davide; Guarnotta Carla; Sozzi Elisa; Zucchetto Antonella; Rigolin Gian Matteo; Fiorcari Stefania; Castelli Ilaria; Fontana Marcella; Coluccio Valeria; Leonardi Giovanna; Zucchini Patrizia; Tripodo Claudio; Cuneo Antonio; Gattei Valter; Del Poeta Giovanni; Forconi Francesco; Gaidano Gianluca; Torelli Giuseppe; Marasca Roberto^*

来源：Blood, 2010, 116(4): 584-592.

DOI：10.1182/blood-2009-11-252494

The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive of reduced TTFT (P < .001) and overall survival (P = .002). Multivariate analysis confirmed that high Ang2 was an independent prognosticator for TTFT (hazard ratio = 1.739; 95% confidence interval, 1.059-2.857; P = .029). Significant associations were found between high Ang2 and advanced Binet stages (P < .001), high beta(2)-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and zeta-chain-associated protein kinase 70 expression (P < 001 and P = .003), and intermediate/high cytogenetic risk (P = .005). Moreover, Ang2 added prognostic power to other conventional prognosticators and helped to refine prognosis among CLL subsets with both high and low vascular endothelial growth factor plasma levels. Ang2 plasma level may be a useful independent prognosticator for CLL. (Blood. 2010; 116(4): 584-592)

• 出版日期2010-7-29