Molecular diagnosis of lymphoid malignancies by gene expression profiling.
Gene expression profiling using DNA microarrays has great potential to improve the understanding, diagnosis, and management of lymphomas, leukemias, and other malignancies. Gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL) have shown that this diagnostic category encompasses at least two molecularly distinct diseases, differing in differentiation stage (cell of origin), oncogenic mechanisms, and clinical outcome. Gene expression profiling revealed that the antiapoptotic NF-kappaB pathway is constitutively active in one DLBCL subgroup, termed activated B cell-like DLBCL, and subsequent studies validated NF-kappaB as a therapeutic target in this type of lymphoma. DNA microarray studies of chronic lymphocytic leukemia (CLL) have led to a gene expression-based predictor that identifies two subtypes of CLL that differ with respect to clinical course and presence of immunoglobulin gene mutations in the CLL cells. These findings underscore the value of gene expression profiling in defining subtypes within the lymphoid malignancies that are molecularly and clinically distinct and argue that this genomic technology should become an integral part of prospective clinical trials.
Davis
R Eric
RE
Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Staudt
Louis M
LM
D004273:DNA, Neoplasm / Q000032:analysis*; D020869:Gene Expression Profiling; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins