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Blood, 15 January 2007, Vol. 109, No. 2, pp. 431-448. Prepublished online as a Blood First Edition Paper on September 7, 2006; DOI 10.1182/blood-2006-06-001149. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-06-001149v1 109/2/431    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 Mrózek, K. Articles by Bloomfield, C. D. Search for Related Content PubMed PubMed Citation Articles by Mrózek, K. Articles by Bloomfield, C. D. Related Collections Oncogenes and Tumor Suppressors Reviews in Translational Hematology Review Articles Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  REVIEWS IN TRANSLATIONAL HEMATOLOGY 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? Krzysztof Mrózek1,, Guido Marcucci1,2, Peter Paschka1, Susan P. Whitman1, and Clara D. Bloomfield1 1 Division of Hematology and Oncology, Department of Internal Medicine, and 2 Division of Human Cancer Genetics, Department of Microbiology, Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio Recent molecular analyses of leukemic blasts from pretreatment marrow or blood of patients with acute myeloid leukemia (AML) and a normal karyotype, the largest cytogenetic subset (ie, 40%-49%) of AML, have revealed a striking heterogeneity with regard to the presence of acquired gene mutations and changes in gene expression. Multiple submicroscopic genetic alterations with prognostic significance have been discovered, including internal tandem duplication of the FLT3 gene, mutations in the NPM1 gene, partial tandem duplication of the MLL gene, high expression of the BAALC gene, and mutations in the CEBPA gene. Application of gene-expression profiling has also identified a gene-expression signature that appears to separate cytogenetically normal AML patients into prognostic subgroups, although gene-expression signature-based classifiers predicting outcome for individual patients with greater accuracy are needed. These and similar future findings are likely to have a major impact on the clinical management of cytogenetically normal AML not only in prognostication but also in selection of appropriate treatment, since many of the identified genetic alterations already constitute or will potentially become targets for specific therapeutic intervention. In this report, we review prognostic genetic findings in karyotypically normal AML and discuss their clinical implications. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Dohner and H. Dohner Molecular characterization of acute myeloid leukemia Haematologica, July 1, 2008; 93(7): 976 - 982. [Full Text] [PDF] W. Blum Post-remission therapy in acute myeloid leukemia: what should I do now? Haematologica, June 1, 2008; 93(6): 801 - 805. [Full Text] [PDF] C. Langer, M. D. Radmacher, A. S. Ruppert, S. P. Whitman, P. Paschka, K. Mrozek, C. D. Baldus, T. Vukosavljevic, C.-G. Liu, M. E. Ross, et al. High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study Blood, June 1, 2008; 111(11): 5371 - 5379. [Abstract] [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] A. Tyybakinoja, E. Elonen, H. Vauhkonen, J. Saarela, and S. 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High Expression Levels of the ETS-Related Gene, ERG, Predict Adverse Outcome and Improve Molecular Risk-Based Classification of Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., August 1, 2007; 25(22): 3337 - 3343. [Abstract] [Full Text] [PDF] S. P. Whitman, A. S. Ruppert, G. Marcucci, K. Mrozek, P. Paschka, C. Langer, C. D. Baldus, J. Wen, T. Vukosavljevic, B. L. Powell, et al. Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study Blood, June 15, 2007; 109(12): 5164 - 5167. [Abstract] [Full Text] [PDF] D. P. Steensma The spectrum of molecular aberrations in myelodysplastic syndromes: in the shadow of acute myeloid leukemia Haematologica, June 1, 2007; 92(6): 723 - 727. [Full Text] [PDF] B. Falini, I. Nicoletti, N. Bolli, M. P. Martelli, A. Liso, P. Gorello, F. Mandelli, C. Mecucci, and M. F. 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