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Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group

AuthorsHaferlach T.; Kohlmann, Alexander; Hernández, Jesús M.
Issue Date2010
PublisherAmerican Society of Clinical Oncology
CitationJournal of Clinical Oncology 28(15): 2529-2537 (2010)
Abstract[Purpose]: The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid malignancies. [Methods]: The investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling–based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients. [Results]: On the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods. [Conclusion]: Gene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias.
DescriptionPresented in part as oral presentation at the 50th Annual Meeting of the American Society of Hematology, December 6-9, 2008, San Francisco, CA.-- et al.
Identifiersdoi: 10.1200/JCO.2009.23.4732
issn: 0732-183X
e-issn: 1527-7755
Appears in Collections:(IBMCC) Artículos
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