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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1291-1300. Prepublished online as a Blood First Edition Paper on May 7, 2007; DOI 10.1182/blood-2006-10-049783. This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: blood-2006-10-049783v1 110/4/1291    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 Bullinger, L. Articles by Döhner, H. Search for Related Content PubMed PubMed Citation Articles by Bullinger, L. Articles by Döhner, H. Related Collections Neoplasia Gene Expression Genomics Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia Lars Bullinger1, Frank G. Rücker1, Stephan Kurz1, Juan Du1, Claudia Scholl1, Sandrine Sander2, Andrea Corbacioglu1, Claudio Lottaz3, Jürgen Krauter4, Stefan Fröhling1, Arnold Ganser4, Richard F. Schlenk1, Konstanze Döhner1, Jonathan R. Pollack5, and Hartmut Döhner1 1 Department of Internal Medicine III, University of Ulm, Ulm, Germany; 2 Department of Physiological Chemistry, University of Ulm, Ulm, Germany; 3 Department for Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Berlin, Germany; 4 Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; and 5 Department of Pathology, Stanford University, Palo Alto, CA Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biologic and clinical heterogeneity within these cytogenetic groups that is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n = 93) of AML patients with CBF leukemia [(inv (16), n = 55; t(8;21), n = 38)]. By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n = 35) characterized by shorter overall survival times (P = .03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21) subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P = .011 and P = .026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the "favorable" CBF leukemias, antiapoptotic mechanisms and deregulated mTOR signaling and, in the newly defined "unfavorable" subgroup, aberrant MAPK signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biologic basis for the heterogeneity observed in CBF leukemia. 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