6533b852fe1ef96bd12aa501

RESEARCH PRODUCT

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

Davide RossiPatrizia ZucchiniGianluca GaidanoRita SantachiaraStefania FiorcariGian Matteo RigolinIlaria CastelliSilvia MartinelliValter GatteiClaudio TripodoGiovanna LeonardiRossana MaffeiGiovanni Del PoetaCarla GuarnottaFrancesco ForconiGiuseppe TorelliAntonio CuneoMarcella FontanaValeria ColuccioElisa SozziRoberto MarascaAntonella Zucchetto

subject

glycoproteinMaleTime FactorsZAP-70Chronic lymphocytic leukemiavascular endothelial growth factor aBiochemistryGastroenterologyimmunoglobulin heavy chainsAdult Aged Aged; 80 and over Angiopoietin-2; analysis/blood Blood Chemical Analysis Female Humans Leukemia; Lymphocytic; Chronic; B-Cell; blood/diagnosis/mortality/therapy Male Middle Aged Neoadjuvant Therapy Prognosis Survival Analysis Time Factors Tumor Markers; Biological; bloodBlood plasma80 and overChronicTumor MarkersAged 80 and overLeukemiaHematologyHazard ratioprotein kinaseHematologyanalysis/bloodMiddle Agedchronic b-cell leukemiasPrognosisLymphocyticNeoadjuvant TherapyLeukemiaCohortFemaleAdultmedicine.medical_specialtyImmunologyangiopoietins chronic b-cell leukemias chronic lymphocytic leukemia plasma vascular endothelial growth factor a cd38 enzyme-linked immunosorbent assay glycoprotein immunoglobulin heavy chains protein kinaseNOcd38Angiopoietin-2bloodInternal medicinemedicineBiomarkers Tumorchronic lymphocytic leukemia angiopoietin-2.Humansbeta(2)-microglobulinplasmaSurvival analysisblood/diagnosis/mortality/therapyAgedbusiness.industryB-CellCell BiologyBiologicalmedicine.diseaseLeukemia Lymphocytic Chronic B-CellSurvival AnalysisConfidence intervalImmunologychronic lymphocytic leukemiaangiopoietin-2enzyme-linked immunosorbent assaybusinessCLL; angiopoietin-2; beta(2)-microglobulin; ZAP-70; CD38Settore MED/15 - Malattie del SangueangiopoietinsBlood Chemical AnalysisCLLCD38Blood Chemical Analysis; Angiopoietin-2; Humans; Neoadjuvant Therapy; Prognosis; Aged; Aged 80 and over; Leukemia Lymphocytic Chronic B-Cell; Adult; Middle Aged; Tumor Markers Biological; Time Factors; Female; Male; Survival Analysis

description

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.

10.1182/blood-2009-11-252494https://hdl.handle.net/11380/644218