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Blood, 15 January 2006, Vol. 107, No. 2, pp. 769-776. Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-07-2930. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: 2005-07-2930v1 107/2/769    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Holleman, A. Articles by Pieters, R. Search for Related Content PubMed PubMed Citation Articles by Holleman, A. Articles by Pieters, R. Related Collections Neoplasia Apoptosis Gene Expression Genomics Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia Amy Holleman, Monique L. den Boer, Renée X. de Menezes, Meyling H. Cheok, Cheng Cheng, Karin M. Kazemier, Gritta E. Janka-Schaub, Ulrich Göbel, Ulrike B. Graubner, William E. Evans, and Rob Pieters From the Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Center for Human and Clinical Genetics, Leiden University Medical Center, the Netherlands; Departments of Pharmaceutical Sciences and Biostatistics, St Jude Children's Research Hospital, Memphis, TN; German Cooperative Study Group for Acute Lymphoblastic Leukemia (COALL) study group, Hamburg, Germany; Children's University Hospital, Hamburg, Germany; Department of Pediatric Hematology and Oncology, University Medical Center, Heinrich-Heine-University, Düsseldorf, Germany; and Department of Pediatric Oncology; Dr von Haunersches Children's Hospital, University of Munich, Germany. Childhood acute lymphoblastic leukemia (ALL) consists of various subtypes that respond differently to cytotoxic drugs and therefore have a markedly different clinical outcome. We used microarrays to investigate, in 190 children with ALL at initial diagnosis, whether 70 key apoptosis genes were differentially expressed between leukemic subgroups defined by lineage, genetic subtype, in vitro drug resistance, and clinical outcome. The expression of 44 of 70 genes was significantly different in T-versus B-lineage ALL, 22 genes differed in hyperdiploid versus nonhyperdiploid, 16 in TEL-AML1-positive versus-negative, and 13 in E2A-rearranged versus germ-line B-lineage ALL. Expression of MCL1 and DAPK1 was significantly associated with prednisolone sensitivity, whereas BCL2L13, HRK, and TNF were related to L-asparaginase resistance. BCL2L13 overexpression was also associated with unfavorable clinical outcome (P < .001). Multivariate analysis including known risk factors revealed that BCL2L13 expression was an independent prognostic factor (P = .011). The same trend was observed in a validation group of 92 children with ALL treated on a different protocol at St Jude (P = .051). In conclusion, ALL subtypes have a unique expression pattern of apoptosis genes and our data suggest that selective genes are linked to cellular drug resistance and prognosis in childhood B-lineage ALL. (Blood. 2006; 107:769-776) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Bcl-rambo: a maverick of apoptotic genes James Feusner Blood 2006 107: 421. [Full Text] [PDF] This article has been cited by other articles: F. Al-Shakfa, S. Dulucq, I. Brukner, I. Milacic, M. Ansari, P. Beaulieu, A. Moghrabi, C. Laverdiere, S. E. Sallan, L. B. Silverman, et al. DNA Variants in Region for Noncoding Interfering Transcript of Dihydrofolate Reductase Gene and Outcome in Childhood Acute Lymphoblastic Leukemia Clin. Cancer Res., November 15, 2009; 15(22): 6931 - 6938. [Abstract] [Full Text] [PDF] J. J. 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