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Blood, 1 August 2006, Vol. 108, No. 3, pp. 1050-1057. Prepublished online as a Blood First Edition Paper on April 20, 2006; DOI 10.1182/blood-2006-01-0322. This Article Full Text Full Text (PDF) All Versions of this Article: 2006-01-0322v1 108/3/1050    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 Flotho, C. Articles by Campana, D. Search for Related Content PubMed PubMed Citation Articles by Flotho, C. Articles by Campana, D. Related Collections Neoplasia Apoptosis Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2 Christian Flotho, Elaine Coustan-Smith, Deqing Pei, Shotaro Iwamoto, Guangchun Song, Cheng Cheng, Ching-Hon Pui, James R. Downing, and Dario Campana From the Departments of Pathology, Hematology-Oncology, and Biostatistics, St Jude Children's Research Hospital, Memphis, TN; and the University of Tennessee College of Medicine, Memphis, TN. In childhood acute lymphoblastic leukemia (ALL), early response to treatment is a powerful prognostic indicator. To identify genes associated with this response, we analyzed gene expression of diagnostic lymphoblasts from 189 children with ALL and compared the findings with minimal residual disease (MRD) levels on days 19 and 46 of remission induction treatment. After excluding genes associated with genetic subgroups, we identified 17 genes that were significantly associated with MRD. The caspase 8–associated protein 2 (CASP8AP2) gene was studied further because of its reported role in apoptosis and glucocorticoid signaling. In a separate cohort of 99 patients not included in the comparison of gene expression profiles and MRD, low levels of CASP8AP2 expression predicted a lower event-free survival (P = .02) and a higher rate of leukemia relapse (P = .01) and were an independent predictor of outcome. High levels of CASP8AP2 expression were associated with a greater propensity of leukemic lymphoblasts to undergo apoptosis. We conclude that measurement of CASP8AP2 expression at diagnosis offers a means to identify patients whose leukemic cells are highly susceptible to chemotherapy. Therefore, this gene is a strong candidate for inclusion in gene expression arrays specifically designed for leukemia diagnosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Colonel Mustard, with the rope, in the ballroom Bruce M. Camitta Blood 2006 108: 785. [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] M. Kiriyama, Y. Kobayashi, M. Saito, F. Ishikawa, and S. 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Kang, R. X. Menezes, W. Yang, H. Sather, N. P. Moskowitz, D.-J. Min, J. W. Potter, R. Harvey, S. P. Hunger, et al. Gene Expression Signatures Predictive of Early Response and Outcome in High-Risk Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study J. Clin. Oncol., September 20, 2008; 26(27): 4376 - 4384. [Abstract] [Full Text] [PDF] A. Manabe, A. Ohara, D. Hasegawa, K. Koh, T. Saito, N. Kiyokawa, A. Kikuchi, H. Takahashi, K. Ikuta, Y. Hayashi, et al. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group Study L99-15 Haematologica, August 1, 2008; 93(8): 1155 - 1160. [Abstract] [Full Text] [PDF] D. Campana Molecular Determinants of Treatment Response in Acute Lymphoblastic Leukemia Hematology, January 1, 2008; 2008(1): 366 - 373. [Abstract] [Full Text] [PDF] C. Flotho, E. Coustan-Smith, D. Pei, C. Cheng, G. Song, C.-H. Pui, J. R. Downing, and D. Campana A set of genes that regulate cell proliferation predicts treatment outcome in childhood acute lymphoblastic leukemia Blood, August 15, 2007; 110(4): 1271 - 1277. [Abstract] [Full Text] [PDF]

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