TY - JOUR
T1 - Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia
AU - Maffei, Rossana
AU - Martinelli, Silvia
AU - Santachiara, Rita
AU - Rossi, Davide
AU - Guarnotta, Carla
AU - Sozzi, Elisa
AU - Zucchetto, Antonella
AU - Rigolin, Gian Matteo
AU - Fiorcari, Stefania
AU - Castelli, Ilaria
AU - Fontana, Marcella
AU - Coluccio, Valeria
AU - Leonardi, Giovanna
AU - Zucchini, Patrizia
AU - Tripodo, Claudio
AU - Cuneo, Antonio
AU - Gattei, Valter
AU - Del Poeta, Giovanni
AU - Forconi, Francesco
AU - Gaidano, Gianluca
AU - Torelli, Giuseppe
AU - Marasca, Roberto
PY - 2010/7/29
Y1 - 2010/7/29
N2 - 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 β2-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and ζ-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.
AB - 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 β2-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and ζ-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.
UR - http://www.scopus.com/inward/record.url?scp=77954891291&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-11-252494
DO - 10.1182/blood-2009-11-252494
M3 - Article
SN - 0006-4971
VL - 116
SP - 584
EP - 592
JO - Blood
JF - Blood
IS - 4
ER -