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Blood, 16 July 2009, Vol. 114, No. 3, pp. 647-650. Prepublished online as a Blood First Edition Paper on May 20, 2009; DOI 10.1182/blood-2009-02-206722. This Article Full Text Full Text (PDF) Supplemental Methods, Appendices, and Table All Versions of this Article: blood-2009-02-206722v1 114/3/647    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Gutierrez, A. Articles by Look, A. T. PubMed PubMed Citation Articles by Gutierrez, A. Articles by Look, A. T. Related Collections Lymphoid Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Brief report High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia Alejandro Gutierrez1,2, Takaomi Sanda1, Ruta Grebliunaite1, Arkaitz Carracedo3, Leonardo Salmena3, Yebin Ahn1, Suzanne Dahlberg4, Donna Neuberg4, Lisa A. Moreau1, Stuart S. Winter5, Richard Larson6, Jianhua Zhang7, Alexei Protopopov7, Lynda Chin7,8, Pier Paolo Pandolfi3, Lewis B. Silverman1,2, Stephen P. Hunger9, Stephen E. Sallan1,2, and A. Thomas Look1,2 1 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; 2 Division of Hematology/Oncology, Children's Hospital, Boston, MA; 3 Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Boston, MA; 4 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; Departments of 5 Pediatrics and 6 Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM; 7 Center for Applied Cancer Science of the Belfer Institute for Innovative Cancer Science and 8 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; and 9 Center for Cancer and Blood Disorders, Children's Hospital and University of Colorado School of Medicine, Aurora, CO To more comprehensively assess the pathogenic contribution of the PTEN-PI3K-AKT pathway to T-cell acute lymphoblastic leukemia (T-ALL), we examined diagnostic DNA samples from children with T-ALL using array comparative genomic hybridization and sequence analysis. Alterations of PTEN, PI3K, or AKT were identified in 47.7% of 44 cases. There was a striking clustering of PTEN mutations in exon 7 in 12 cases, all of which were predicted to truncate the C2 domain without disrupting the phosphatase domain of PTEN. Induction chemotherapy failed to induce remission in 3 of the 4 patients whose lymphoblasts harbored PTEN deletions at the time of diagnosis, compared with none of the 12 patients with mutations of PTEN exon 7 (P = .007), suggesting that PTEN deletion has more adverse therapeutic consequences than mutational disruptions that preserve the phosphatase domain. These findings add significant support to the rationale for the development of therapies targeting the PTEN-PI3K-AKT pathway in T-ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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