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.

CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities / 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. - In: LEUKEMIA RESEARCH. - ISSN 0145-2126. - STAMPA. - 41:(2016), pp. 36-42. [10.1016/j.leukres.2015.11.018]

CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities

LUPPI, Mario;
2016

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.
23-dic-2015
41
36
42
CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities / 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. - In: LEUKEMIA RESEARCH. - ISSN 0145-2126. - STAMPA. - 41:(2016), pp. 36-42. [10.1016/j.leukres.2015.11.018]
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
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1105726
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