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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1435-1441. Prepublished online as a Blood First Edition Paper on May 13, 2004; DOI 10.1182/blood-2003-12-4306. This Article Full Text (PDF) Supplemental Data All Versions of this Article: 2003-12-4306v1 104/5/1435    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 Zaza, G. Articles by Evans, W. E Search for Related Content PubMed PubMed Citation Articles by Zaza, G. Articles by Evans, W. E Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 18, 2003 Accepted April 7, 2004 Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes involved in purine metabolism and lower de novo purine synthesis Gianluigi Zaza, Wenjian Yang, Leo Kager, Meyling Cheok, James Downing, Ching-Hon Pui, Cheng Cheng, Mary V Relling, and William E Evans* Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; Division of Nephrology, University of Bari, Bari, Italy Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA; Hematology Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Clinical Pharmacy, University of Tennessee, Memphis, Memphis, TN, USA Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; Clinical Pharmacy, University of Tennessee, Memphis, Memphis, TN, USA * Corresponding author; email: william.evans{at}stjude.org. Because de novo purine synthesis (DNPS) is a target of widely used antileukemic agents (e.g., methotrexate, mercaptopurine), we determined the rate of DNPS and the expression of genes involved in purine metabolism, in different subtypes of acute lymphoblastic leukemia (ALL). Among 113 children with newly diagnosed ALL, lymphoblasts with the TEL-AML1 translocation had significantly lower DNPS than all other genetic subtypes of B-lineage ALL or T-lineage ALL (352±57 versus 1001±31 or versus 1315±76 fmol/nmol/h, p<0.0001). By assessing the expression of 82 genes involved in purine metabolism (KEGG pathway database) in ALL blasts from 38 patients with B-lineage ALL (14 with TEL-AML1, 24 without), we identified 16 genes that were differentially expressed in TEL-AML1 positive and TEL-AML1 negative ALL (p<0.001, FDR=5%). The pattern of expression of these 16 genes discriminated TEL-AML1 positive ALL, with a true accuracy of 84% in an independent test-set (N=17, C.I. 70%-94%, p<0.001). Western blots of selected genes documented corresponding levels of the proteins encoded. Differentially expressed genes included HPRT, IMPDH, PAICS and GART, all of which were expressed at a significantly lower level in TEL-AML1 ALL. These findings have established that TEL-AML1 ALL has significantly lower de novo purine synthesis and differential expression of genes involved in purine metabolism. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Targeting ALL leukemia Jerald P. Radich Blood 2004 104: 1235-1236. [Full Text] [PDF] This article has been cited by other articles: A. Andersson, T. Olofsson, D. Lindgren, B. Nilsson, C. Ritz, P. Eden, C. Lassen, J. Rade, M. Fontes, H. Morse, et al. Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations PNAS, December 27, 2005; 102(52): 19069 - 19074. [Abstract] [Full Text] [PDF]

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