Gene expression profiling in follicular lymphoma to assess clinical aggressiveness and to guide the choice of treatment

• Published in: Blood Vol. 105; no. 1; pp. 301 - 307
• Main Authors: Glas, Annuska M., Kersten, Marie José, Delahaye, Leonie J.M.J., Witteveen, Anke T., Kibbelaar, Robby E., Velds, Arno, Wessels, Lodewyk F.A., Joosten, Peter, Kerkhoven, Ron M., Bernards, René, van Krieken, Johan H.J.M., Kluin, Philip M., van't Veer, Laura J., de Jong, Daphne
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-01-2005; The Americain Society of Hematology
• Subjects: Adult; Aged; Biological and medical sciences; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Follicular - classification; Lymphoma, Follicular - diagnosis; Lymphoma, Follicular - genetics; Lymphoma, Follicular - therapy; Medical sciences; Middle Aged; Neoplasm Proteins - genetics; Prognosis; Recurrence; Reproducibility of Results; Human; Choice; Acute; Stage classification; Biological marker; Malignant hemopathy; Malignancy; Method; Non Hodgkin lymphoma; High grade; Gene expression profile; Treatment; Gene; Lymphoproliferative syndrome; Follicular lymphoma; Genetics; Aggressiveness; Low grade
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-06-2298

Follicular lymphoma (FL) is a disease characterized by a long clinical course marked by frequent relapses that vary in clinical aggressiveness over time. Therefore, the main dilemma at each relapse is the choice for the most effective treatment for optimal disease control and failure-free survival while at the same time avoiding overtreatment and harmful side effects. The selection for more aggressive treatment is currently based on histologic grading and clinical criteria; however, in up to 30% of all cases these methods prove to be insufficient. Using supervised classification on a training set of paired samples from patients who experienced either an indolent or aggressive disease course, a gene expression profile of 81 genes was established that could, with an accuracy of 100%, distinguish low-grade from high-grade disease. This profile accurately classified 93% of the FL samples in an independent validation set. Most important, in a third series of FL cases where histologic grading was ambiguous, precluding meaningful morphologic guidance, the 81-gene profile shows a classification accuracy of 94%. The FL stratification profile is a more reliable marker of clinical behavior than the currently used histologic grading and clinical criteria and may provide an important alternative to guide the choice of therapy in patients with FL both at presentation and at relapse. (Blood. 2005;105:301-307)