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

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)584-592
Number of pages9
JournalBlood
Volume116
Issue number4
DOIs
Publication statusPublished - Jul 29 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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