CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities. (February 2016)

• Record Type: Journal Article
• Authors: Chiaretti, Sabina; Brugnoletti, Fulvia; Messina, Monica; Paoloni, Francesca; Fedullo, Anna Lucia; Piciocchi, Alfonso; Elia, Loredana; Vitale, Antonella; Mauro, Elisa; Ferrara, Felicetto; De Fabritiis, Paolo; Luppi, Mario; Ronco, Francesca; De Propris, Maria Stefania; Raponi, Sara; Kronnie, Geertruy te; Vignetti, Marco; Guarini, Anna; Foà, Robin
• Is Part Of: Leukemia research. Volume 41(2016:Feb.)
• Page Start: 36
• Page End: 42
• Publication Date: 2016-02
• Subjects: CRLF2 overexpression -- Acute lymphoblastic leukemia -- Adult patients -- Prognosis; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2015.11.018
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: 34% of adult B-lineage ALL without aberrations have high CRLF2 expression levels. In adult B-ALL, CRLF2 expression has prognostic significance. Also in adult B-ALL, CRLF2 is associated with JAK/STAT and IKZF1 lesions. Abstract: Background: A deregulated CRLF2 (d- CRLF2 ) expression was described in B-cell acute lymphoblastic leukemia without recurrent fusion genes (B-NEG ALL). While the role of d- CRLF2 in children has been extensively described, little is known about its role and impact in adult ALL. Methods: Expression levels of CRLF2 were evaluated by quantitative real-time PCR in 102 newly-diagnosed adult B-NEG ALL and correlated with the clinico-biological characteristics and outcome. Incidence and clinical impact of the P2RY8/CRLF2 transcript was also assessed. Results: High CRLF2 levels, as continuous variable, were significantly associated with hyperleucocytosis ( p = 0.0002) and thrombocytopenia ( p = 0.005); when a cut-point at ΔCt ≤ 8 was applied, 35 cases (34.3%), mostly males (80%), proved positive for CRLF2 expression. High CRLF2 levels, as continuous or categorical variable, were associated with a worse disease-free ( p = 0.003 and p = 0.015) and overall survival ( p = 0.017 and 0.0038). Furthermore, when CRLF2 was analyzed as a categorical variable, a high statistical association was found with IKZF1 deletion and mutations in the JAK/STAT pathway ( p = 0.001 and p < 0.0001, respectively). Finally, the P2RY8/CRLF2 transcript, identified in 8/102 patients (7.8%), was associated with a poor outcome. Conclusions: In adult B-NEG ALL, high CRLF2 expression is associated with distinct clinico-biological features and an unfavourable prognosis in both univariate and multivariate analysis; similarly, P2RY8/CRLF2 positivity correlates with a poor outcome. The quantification of CRLF2 is an important prognostic marker in adult B-lineage ALL without known genetic lesions.