ABSTRACT

Introduction 380 DNA microarrays 380 Biostatistical analysis methods 380 Commonly used terms and definitions 382 Applications of gene expression profile analysis 382 Classification of lymphoid malignancies 383 Diffuse large B cell lymphoma 383 B cell chronic lymphocytic leukemia 383 Acute lymphoblastic leukemia 386 Other lymphoid malignancies 386 Relation of lymphoid malignancies to their normal 386

cell of origin

Diffuse large B cell lymphoma 387 B cell chronic lymphocytic leukemia 387 Other lymphoid malignancies 387 Insights into pathogenetic mechanisms of lymphoma 388

development Identification of tumor-specific gene expression 389 Dissecting cellular pathways in normal and 389

transformed cells Key points 390 References 390

Global gene expression profile (GEP) analysis, facilitated by the invention of DNA microarrays in the late 1990s that allowed the simultaneous screening of thousands of expressed genes, was poised from the beginning to have a major impact on the classification of the lymphoid neoplasms. While previously only relatively few cell-surface antigens or other markers, often in combination with morphological features, were used for the phenotypic characterization of lymphoid tumors, GEP analysis generates an enormous number of data points that become available for a more comprehensive comparative analysis of tumor entities. These methodological advances allow progress in a number of issues, including the identification of novel tumor subtypes, the cellular derivation of tumors, and the identification of tumor-associated gene expression patterns of potential therapeutic value.