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CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia.
Palmi, Chiara; Savino, Angela M; Silvestri, Daniela; Bronzini, Ilaria; Cario, Gunnar; Paganin, Maddalena; Buldini, Barbara; Galbiati, Marta; Muckenthaler, Martina U; Bugarin, Cristina; Della Mina, Pamela; Nagel, Stefan; Barisone, Elena; Casale, Fiorina; Locatelli, Franco; Lo Nigro, Luca; Micalizzi, Concetta; Parasole, Rosanna; Pession, Andrea; Putti, Maria C; Santoro, Nicola; Testi, Anna M; Ziino, Ottavio; Kulozik, Andreas E; Zimmermann, Martin; Schrappe, Martin; Villa, Antonello; Gaipa, Giuseppe; Basso, Giuseppe; Biondi, Andrea; Valsecchi, Maria G; Stanulla, Martin; Conter, Valentino; Te Kronnie, Geertruy; Cazzaniga, Giovanni.
Afiliação
  • Palmi C; Centro Ricerca M. Tettamanti, Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Savino AM; Centro Ricerca M. Tettamanti, Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Silvestri D; Center of Biostatistics for Clinical Epidemiology, Department of Health Sciences, University of Milano-Bicocca, Milan, Italy.
  • Bronzini I; Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Cario G; Laboratory of Onco-Hematology, Department SDB, Università di Padova, Padova, Italy.
  • Paganin M; Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • Buldini B; Laboratory of Onco-Hematology, Department SDB, Università di Padova, Padova, Italy.
  • Galbiati M; Laboratory of Onco-Hematology, Department SDB, Università di Padova, Padova, Italy.
  • Muckenthaler MU; Centro Ricerca M. Tettamanti, Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Bugarin C; Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg and EMBL/Medical Faculty Molecular Medicine Partnership Unit, Heidelberg, Germany.
  • Della Mina P; Centro Ricerca M. Tettamanti, Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Nagel S; Microscopy and Image Analysis Consortium, Università di Milano-Bicocca, Monza, Italy.
  • Barisone E; Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
  • Casale F; Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy.
  • Locatelli F; Pediatric Oncology Service, Pediatric Department of 2nd University of Naples, Naples, Italy.
  • Lo Nigro L; Department of Pediatric Hematology/Oncology, IRCCS Ospedale Bambino Gesù, Rome - University of Pavia, Pavia, Italy.
  • Micalizzi C; Center of Pediatric Hematology Oncology, Azienda Ospedaliero-Universitaria "Policlinico Vittorio Emanuele", Catania, Italy.
  • Parasole R; Hematology/Oncology Unit, G. Gaslini Children's Hospital, Genoa, Italy.
  • Pession A; Department of Pediatric Hemato-Oncology, Ospedale Pausilipon, Napoli, Italy.
  • Putti MC; Department of Pediatrics, "Lalla Seràgnoli" Hematology-Oncology Unit, University of Bologna, Bologna, Italy.
  • Santoro N; Laboratory of Onco-Hematology, Department SDB, Università di Padova, Padova, Italy.
  • Testi AM; Department of Pediatrics, Division of Pediatric Hematology-Oncology, University "A. Moro" of Bari, Bari, Italy.
  • Ziino O; Division of Hematology, Department of Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy.
  • Kulozik AE; Pediatric Hematology and Oncology Unit, A.R.N.A.S. Civico, Di Cristina and Benfratelli Hospital, Palermo, Italy.
  • Zimmermann M; Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg and EMBL/Medical Faculty Molecular Medicine Partnership Unit, Heidelberg, Germany.
  • Schrappe M; Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany.
  • Villa A; Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • Gaipa G; Microscopy and Image Analysis Consortium, Università di Milano-Bicocca, Monza, Italy.
  • Basso G; Centro Ricerca M. Tettamanti, Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Biondi A; Laboratory of Onco-Hematology, Department SDB, Università di Padova, Padova, Italy.
  • Valsecchi MG; Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Stanulla M; Center of Biostatistics for Clinical Epidemiology, Department of Health Sciences, University of Milano-Bicocca, Milan, Italy.
  • Conter V; Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany.
  • Te Kronnie G; Clinica Pediatrica, Università di Milano Bicocca, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy.
  • Cazzaniga G; Laboratory of Onco-Hematology, Department SDB, Università di Padova, Padova, Italy.
Oncotarget ; 7(37): 59260-59272, 2016 Sep 13.
Article em En | MEDLINE | ID: mdl-27449287
Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL.We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers.Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated.Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib.In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Biomarcadores Tumorais / Receptores de Citocinas / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Biomarcadores Tumorais / Receptores de Citocinas / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2016 Tipo de documento: Article