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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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Gutierrez, A. Articles by Look, A. T. Search for Related Content PubMed PubMed Citation Articles by Gutierrez, A. Articles by Look, A. T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 25, 2009 Accepted May 3, 2009 High frequency of PTEN, PI3K and AKT abnormalities in T cell acute lymphoblastic leukemia Alejandro Gutierrez, Takaomi Sanda, Ruta Grebliunaite, Arkaitz Carracedo, Leonardo Salmena, Yebin Ahn, Suzanne Dahlberg, Donna Neuberg, Lisa A. Moreau, Stuart S. Winter, Richard Larson, Jianhua Zhang, Alexei Protopopov, Lynda Chin, Pier Paolo Pandolfi, Lewis B. Silverman, Stephen P. Hunger, Stephen E. Sallan, and A. Thomas Look* Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Boston, MA, United States Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, United States Department of Pediatrics, The University of New Mexico Health Sciences Center, Albuquerque, NM, United States Department of Pathology, The University of New Mexico Health Sciences Center, Albuquerque, NM, United States Center for Applied Cancer Science of the Belfer Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Boston, MA, United States Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Division of Hematology/Oncology, Children's Hospital Boston, Boston, MA, United States Center for Cancer and Blood Disorders, The Children's Hospital and University of Colorado School of Medicine, Aurora, CO, United States * Corresponding author; email: thomas_look{at}dfci.harvard.edu. 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 CGH 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 = 0.007), 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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