Sabina Chiaretti1, Fulvia Brugnoletti1, Monica Messina1, Francesca Paoloni2, Anna Lucia Fedullo1, Alfonso Piciocchi2, Loredana Elia1, Antonella Vitale1, Elisa Mauro3, Felicetto Ferrara4, Paolo De Fabritiis5, Mario Luppi6, Francesca Ronco7, Maria Stefania De Propris1, Sara Raponi1, Geertruy Te Kronnie8, Marco Vignetti2, Anna Guarini1, Robin Foà9. 1. Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Italy. 2. GIMEMA Data Center, Rome, Italy. 3. Division of Hematology, AOU Policlinico-OVE, University of Catania, Italy. 4. Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy. 5. Hematology, Sant'Eugenio Hospital, Rome, Italy. 6. Hematology Division, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy. 7. Hematology Unit, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy. 8. Laboratory of Oncohematology, Department of Women's and Children's Health, University of Padova, Italy. 9. Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Italy. Electronic address: rfoa@bce.uniroma1.it.
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.
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.
Authors: Kai Lee Yap; Larissa V Furtado; Kazuma Kiyotani; Emily Curran; Wendy Stock; Jennifer L McNeer; Sabah Kadri; Jeremy P Segal; Yusuke Nakamura; Michelle M Le Beau; Sandeep Gurbuxani; Gordana Raca Journal: Leuk Lymphoma Date: 2016-11-17
Authors: Sabina Chiaretti; Monica Messina; Sara Grammatico; Alfonso Piciocchi; Anna L Fedullo; Filomena Di Giacomo; Nadia Peragine; Valentina Gianfelici; Alessia Lauretti; Rohan Bareja; Maria P Martelli; Marco Vignetti; Valerio Apicella; Antonella Vitale; Loretta S Li; Cyril Salek; Olivier Elemento; Giorgio Inghirami; David M Weinstock; Anna Guarini; Robin Foà Journal: Br J Haematol Date: 2018-04-19 Impact factor: 6.998
Authors: Maribel Forero-Castro; Cristina Robledo; Rocío Benito; Irene Bodega-Mayor; Inmaculada Rapado; María Hernández-Sánchez; María Abáigar; Jesús Maria Hernández-Sánchez; Miguel Quijada-Álamo; José María Sánchez-Pina; Mónica Sala-Valdés; Fernanda Araujo-Silva; Alexander Kohlmann; José Luis Fuster; Maryam Arefi; Natalia de Las Heras; Susana Riesco; Juan N Rodríguez; Lourdes Hermosín; Jordi Ribera; Mireia Camos Guijosa; Manuel Ramírez; Cristina Díaz de Heredia Rubio; Eva Barragán; Joaquín Martínez; José M Ribera; Elena Fernández-Ruiz; Jesús-María Hernández-Rivas Journal: Br J Cancer Date: 2017-05-30 Impact factor: 7.640