title: Molecular signatures in the diagnosis and management of diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  This review summarizes recent data on the relevance of molecular subtypes of diffuse large B-cell lymphoma to clinical management and the potential to use subtyping to direct therapy.
  
  
  RESULTS
  Gene expression profiling and immunohistochemistry can distinguish between diffuse large B-cell lymphomas arising from germinal center-derived B-cells (GCB type) or activated B-cells (ABC type) with a high degree of concordance. This biologic distinction is highly relevant clinically. The ABC type is associated with a poor prognosis and is characterized biologically by constitutive activation of the NF-κB pathway and chronic activation of the B-cell receptor pathway, both of which confer an antiapoptotic phenotype and chemoresistance. Emerging preclinical and clinical data suggest that these pathways can be targeted specifically in ABC-type disease. New molecular techniques may allow further refinement of this approach.
  
  
  CONCLUSIONS
  Recent data support the concept that molecular subtyping of diffuse large B-cell lymphoma is clinically relevant and likely to be incorporated into diagnostic and therapeutic algorithms. The availability of widely applicable and reproducible techniques for determining molecular subtype will be essential.
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Cleveland, Ohio 44195, USA. sweetej@ccf.org
authors.forename: John W
authors.initials: JW
authors.lastname: Sweetenham
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D058990:Molecular Targeted Therapy