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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1677-1683. Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2006-02-005538. This Article Full Text (PDF) Supplemental Data All Versions of this Article: blood-2006-02-005538v1 108/5/1677    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 Radmacher, M. D Articles by Bloomfield, C. D Search for Related Content PubMed PubMed Citation Articles by Radmacher, M. D Articles by Bloomfield, C. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2006 Accepted April 21, 2006 Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: A cancer and leukemia group B study Michael D Radmacher, Guido Marcucci, Amy S Ruppert, Krzysztof Mrozek, Susan P Whitman, James W Vardiman, Peter Paschka, Tamara Vukosavljevic, Claudia D Baldus, Jonathan E Kolitz, Michael A Caligiuri, Richard A Larson, and Clara D Bloomfield* Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University,Columbus Ohio Division of Hematology and Oncology, Department of Internal Medicine, Ohio State UnivUniversity University of Chicago, Chicago, IL, USA Charite, Campus Benjamin Franklin, Medizinische Klinik III, Berlin, Germany North Shore University Hospital, Manhasset, NY * Corresponding author; email: clara.bloomfield{at}osumc.edu. Patients with acute myeloid leukemia (AML) and normal karyotype are classified in an intermediate-risk group, albeit this subset is heterogeneous for clinical outcome. A recent complementary-DNA microarray study identified a gene-expression signature that-- when used to cluster normal karyotype patients-- separated them into two prognostically relevant subgroups. We sought the first independent validation of the prognostic value of this signature. Using oligonucleotide microarrays to measure gene expression in samples from uniformly treated adults with karyotypically normal AML, we performed cluster analysis based on the previously identified signature. We also developed a well-defined classification rule using the signature to predict outcome for individual patients. Cluster analysis confirmed the prognostic utility of the signature: patient clusters differed in overall (P=0.001) and disease-free (P=0.001) survival. The signature-based classifier identified groups with differences in overall (P=0.02) and disease-free (P=0.05) survival. A strong association of the outcome classifier with the prognostically adverse FLT3 internal tandem duplication (FLT3 ITD) potentially explained the prognostic significance of the signature. However, in the subgroup of patients without FLT3 ITD there was a moderate difference in survival for the classifier-derived groups. Our analysis confirms the applicability of the gene-expression profiling strategy for outcome prediction in cytogenetically normal AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. M. Santamaria, M. C. Chillon, R. Garcia-Sanz, C. Perez, M. D. Caballero, F. Ramos, A. G. de Coca, J. M. Alonso, P. Giraldo, T. Bernal, et al. Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia Blood, July 2, 2009; 114(1): 148 - 152. [Abstract] [Full Text] [PDF] C. Langer, G. Marcucci, K. B. Holland, M. D. Radmacher, K. Maharry, P. Paschka, S. P. Whitman, K. Mrozek, C. D. Baldus, R. Vij, et al. Prognostic Importance of MN1 Transcript Levels, and Biologic Insights From MN1-Associated Gene and MicroRNA Expression Signatures in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., July 1, 2009; 27(19): 3198 - 3204. [Abstract] [Full Text] [PDF] U. Bacher, A. Kohlmann, and T. Haferlach Perspectives of gene expression profiling for diagnosis and therapy in haematological malignancies Brief Funct Genomic Proteomic, May 27, 2009; (2009) elp011v1. [Abstract] [Full Text] [PDF] S. Faderl, A. Pal, W. Bornmann, M. Albitar, D. Maxwell, Q. Van, Z. Peng, D. Harris, Z. Liu, I. Hazan-Halevy, et al. Kit Inhibitor APcK110 Induces Apoptosis and Inhibits Proliferation of Acute Myeloid Leukemia Cells Cancer Res., May 1, 2009; 69(9): 3910 - 3917. [Abstract] [Full Text] [PDF] B. J. Wouters, B. 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Blum Post-remission therapy in acute myeloid leukemia: what should I do now? Haematologica, June 1, 2008; 93(6): 801 - 805. [Full Text] [PDF] J. E. Karp, B. D. Smith, I. Gojo, J. E. Lancet, J. Greer, M. Klein, L. Morris, M. J. Levis, S. D. Gore, J. J. Wright, et al. Phase II Trial of Tipifarnib as Maintenance Therapy in First Complete Remission in Adults with Acute Myelogenous Leukemia and Poor-Risk Features Clin. Cancer Res., May 15, 2008; 14(10): 3077 - 3082. [Abstract] [Full Text] [PDF] G. Marcucci, M. D. Radmacher, K. Maharry, K. Mrozek, A. S. Ruppert, P. Paschka, T. Vukosavljevic, S. P. Whitman, C. D. Baldus, C. Langer, et al. MicroRNA Expression in Cytogenetically Normal Acute Myeloid Leukemia N. Engl. J. Med., May 1, 2008; 358(18): 1919 - 1928. [Abstract] [Full Text] [PDF] L. Bullinger, K. Dohner, R. Kranz, C. Stirner, S. Frohling, C. Scholl, Y. H. Kim, R. F. Schlenk, R. Tibshirani, H. Dohner, et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML Blood, May 1, 2008; 111(9): 4490 - 4495. [Abstract] [Full Text] [PDF] M. Raponi, J. E. Lancet, H. Fan, L. Dossey, G. Lee, I. Gojo, E. J. Feldman, J. Gotlib, L. E. Morris, P. L. Greenberg, et al. A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia Blood, March 1, 2008; 111(5): 2589 - 2596. [Abstract] [Full Text] [PDF] J. R. Pollack A Perspective on DNA Microarrays in Pathology Research and Practice Am. J. Pathol., August 1, 2007; 171(2): 375 - 385. [Abstract] [Full Text] [PDF] K. Mrozek, G. Marcucci, P. Paschka, S. P. Whitman, and C. D. Bloomfield Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood, January 15, 2007; 109(2): 431 - 448. [Abstract] [Full Text] [PDF] K. Mrozek and C. D. Bloomfield Chromosome Aberrations, Gene Mutations and Expression Changes, and Prognosis in Adult Acute Myeloid Leukemia Hematology, January 1, 2006; 2006(1): 169 - 177. [Abstract] [Full Text] [PDF]

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