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Blood, 1 June 2008, Vol. 111, No. 11, pp. 5371-5379. Prepublished online as a Blood First Edition Paper on March 31, 2008; DOI 10.1182/blood-2007-11-124958. This Article Full Text Full Text (PDF) Supplemental Methods, Appendix, Tables, and Figures All Versions of this Article: blood-2007-11-124958v1 111/11/5371    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 CrossRef Google Scholar Articles by Langer, C. Articles by Bloomfield, C. D. PubMed PubMed Citation Articles by Langer, C. Articles by Bloomfield, C. D. Related Collections Free Research Articles Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 Christian Langer1,2, Michael D. Radmacher1,3, Amy S. Ruppert1,3, Susan P. Whitman1, Peter Paschka1, Krzysztof Mrózek1, Claudia D. Baldus4, Tamara Vukosavljevic1, Chang-Gong Liu2, Mary E. Ross5, Bayard L. Powell6, Albert de la Chapelle2, Jonathan E. Kolitz7, Richard A. Larson8, Guido Marcucci1,2, and Clara D. Bloomfield1 1 Division of Hematology and Oncology, Department of Internal Medicine; and 2 Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus; 3 The Cancer and Leukemia Group B (CALGB) Statistical Center, Duke University Medical Center, Durham, NC; 4 Department of Hematology and Oncology, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany; 5 Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Columbus, OH; 6 Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC; 7 Department of Medicine, North Shore University Hospital, Manhasset, NY; and 8 Department of Medicine, University of Chicago, IL BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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