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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3434-3441. Prepublished online as a Blood First Edition Paper on January 13, 2005; DOI 10.1182/blood-2004-07-2922. This Article Full Text (PDF) All Versions of this Article: 2004-07-2922v1 105/9/3434    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mancini, M. Articles by Foa, R. Search for Related Content PubMed PubMed Citation Articles by Mancini, M. Articles by Foa, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 28, 2004 Accepted December 24, 2004 A comprehensive genetic classification of adult Acute Lymphoblastic Leukemia (ALL): Analysis of the GIMEMA 0496 protocol Marco Mancini*, Daniela Scappaticci, Giuseppe Cimino, Mauro Nanni, Valentina Derme, Loredana Elia, Agostino Tafuri, Marco Vignetti, Antonella Vitale, Antonio Cuneo, Gianluigi Castoldi, Giuseppe Saglio, Fabrizio Pane, Cristina Mecucci, Andrea Camera, Giorgina Specchia, Alessandra Tedeschi, Francesco Di Raimondo, Giuseppe Fioritoni, Salvatore Mirto, Filippo Marmont, Felicetto Ferrara, Nicola Cascavilla, Giuseppe Todeschini, Francesco Nobile, Maria G Kropp, Pietro Leoni, Antonio Tabilio, Mario Luppi, Luciana Annino, Franco Mandelli, and Robin Foa Department of Cellular Biotechnologies and Hematology, University 'La Sapienza', Rome, Italy Dipartimento di Scienze Biomediche e Terapie Avanzate, Sezione di Ematologia, Universita di Ferrara, Ferrara, Italy Division of Hematology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy CEINGE Biotecnologie Avanzate, Department of Biochemistry and Medical Biotechnology, Federico II University, Naples, Italy Hematology and Bone Marrow Trasplantation Unit, University of Perugia, Perugia, Italy Hematology, Federico II University, Naples, Italy Department of Hematology, University of Bari, Bari, Jamaica Hematology, Niguarda Ca Granda Hospital, Milan, Italy Department of Medical Sciences, University of Catania, Catania, Italy Hematology, Civil Hospital, Pescara, Italy Hematology, Hospital Cervello, Palermo, Italy Department of Medicine, Hospital S. Giovanni Battista, Torino, Italy Hematology, Cardarelli Hospital, Naples, Italy Hematology, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy Divisione di Ematologia, Azienda Ospedaliera, Reggio Calabria, Italy Hematology, Azienda Ospedaliera A. Pugliese, Catanzaro, Italy Hematology, University of Ancona, Ancona, Italy Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy Azienda Ospedaliera S. Giovanni Addolorata, Roma, Italy * Corresponding author; email: mancini{at}bce.uniroma1.it. The GIMEMA 0496 protocol through the central handling of bone marrow samples at presentation has enabled a unique opportunity to combine the cytogenetic and molecular information on a high number of adult ALL patients, allowing to define as broadly as possible their genetic profile and to determine the impact on outcome of the pretreatment cytogenetic-molecular signature of a large series of patients treated homogeneously. Of 414 patients centrally processed, 325 could be considered for the categorization into the following cytogenetic-molecular subgroups: normal, t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1;19)/E2A-PBX1, 9p/p15-p16 deletions, 6q deletions, miscellaneous structural abnormalities and hyperdiploid. The inclusion of the patients into each subgroup was based arbitrarily on a hierarchical approach: molecular abnormalities with adverse prognostic significance had precedence over karyotypic structural changes with less defined prognosis and the latter over ploidy. Based on the disease-free survival (DFS) probability, 3 cytogenetic-molecular prognostic groups could be defined. Patients without genetic abnormalities and those with isolated 9p/p15-p16 deletions showed a relatively favorable outcome (median DFS >3 years). The t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1;19)/E2A-PBX1 defined a group with highly adverse prognosis (median DFS 7 months), whereas 6q deletions, other miscellaneous structural aberrations and hyperdiploidy predicted an intermediate prognosis (median DFS 19 months). This study highlights the importance of a combined cytogenetic-molecular profiling of adult ALL at presentation as a critical independent determinant of their outcome, providing further evidence of the necessity of a risk-adapted therapeutic algorithm for an optimal management of these patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Trageser, I. Iacobucci, R. Nahar, C. 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