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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1271-1277. Prepublished online as a Blood First Edition Paper on April 24, 2007; DOI 10.1182/blood-2007-01-068478. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: blood-2007-01-068478v1 110/4/1271    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 Gene Expression Genomics Clinical Trials and Observations Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A set of genes that regulate cell proliferation predicts treatment outcome in childhood acute lymphoblastic leukemia Christian Flotho1, Elaine Coustan-Smith2, Deqing Pei3, Cheng Cheng3, Guangchun Song1, Ching-Hon Pui1,2,4, James R. Downing1,4, and Dario Campana1,2,4 Departments of1 Pathology 2 Oncology, and 3 Biostatistics, St Jude Children's Research Hospital, Memphis, TN; 4 University of Tennessee College of Medicine, Memphis To identify novel predictors of outcome in childhood acute lymphoblastic leukemia (ALL), we analyzed gene expression in the leukemic cells of 187 children with newly diagnosed ALL and compared the findings with minimal residual disease (MRD) results obtained on day 19 of remission induction treatment. Genes that showed a significant relationship to MRD were then tested for their capacity to predict leukemic relapse in an independent cohort of 99 patients. We identified 674 probe sets that were associated with MRD on day 19 (P < .006); 40 of the identified genes predicted relapse (P < .03). Among these, 14 showed independent prognostic significance after adjustment for age, leukocyte count at diagnosis, and genetic subtype. More than half of the 40 genes and nearly all of the 14 genes were functionally related, as indicated by their roles in the regulation of cell proliferation. Underexpression of genes promoting cell proliferation was associated with resistance to chemotherapy. The biologic processes regulated by the genes we identified appear to be key determinants of the early cytoreductive response to remission induction therapy and subsequent clinical outcome in childhood ALL. Incorporation of the expression levels of these genes into existing strategies of risk classification could improve clinical management. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Response: Genes associated with response to therapy in childhood acute lymphoblastic leukemia Christian Flotho, Elaine Coustan-Smith, Deqing Pei, Cheng Cheng, Guangchun Song, Ching-Hon Pui, James R. Downing, and Dario Campana Blood 2008 111: 2487-2488. [Full Text] [PDF] Significance of PRDM1β expression as a prognostic marker in diffuse large B-cell lymphomas Wayne Tam, Mario Gomez, and Kui Nie Blood 2008 111: 2488-2489. [Full Text] [PDF] This article has been cited by other articles: J. E. Rubnitz, M. Onciu, S. Pounds, S. Shurtleff, X. Cao, S. C. Raimondi, F. G. Behm, D. Campana, B. I. Razzouk, R. C. Ribeiro, et al. Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital Blood, May 21, 2009; 113(21): 5083 - 5089. [Abstract] [Full Text] [PDF] L. Milani, A. Lundmark, J. Nordlund, A. Kiialainen, T. Flaegstad, G. Jonmundsson, J. Kanerva, K. Schmiegelow, K. L. Gunderson, G. Lonnerholm, et al. Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation Genome Res., January 1, 2009; 19(1): 1 - 11. [Abstract] [Full Text] [PDF] E. Marston, V. Weston, J. Jesson, E. Maina, C. McConville, A. Agathanggelou, A. Skowronska, K. Mapp, K. Sameith, J. E. Powell, et al. Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response Blood, January 1, 2009; 113(1): 117 - 126. [Abstract] [Full Text] [PDF] B. I. Sikic, R. Tibshirani, and N. J. Lacayo Genomics of Childhood Leukemias: The Virtue of Complexity J. Clin. Oncol., September 20, 2008; 26(27): 4367 - 4368. [Full Text] [PDF] D. Bhojwani, H. 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] C. Flotho, E. Coustan-Smith, D. Pei, C. Cheng, G. Song, C.-H. Pui, J. R. Downing, and D. Campana Response: Genes associated with response to therapy in childhood acute lymphoblastic leukemia Blood, February 15, 2008; 111(4): 2487 - 2488. [Full Text] [PDF] D. Catchpoole, D. Guo, H. Jiang, and C. Biesheuvel Predicting outcome in childhood acute lymphoblastic leukemia using gene expression profiling: Prognostication or protocol selection? Blood, February 15, 2008; 111(4): 2486 - 2487. [Full Text] [PDF] D. 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