title: High Myc activity is an independent negative prognostic factor for diffuse large B cell lymphomas.
abstract: Gene expression profiling has recently enabled the reclassification of aggressive non-Hodgkin lymphomas (aNHL) into distinct subgroups. In Burkitt lymphoma (BL) aberrant c-Myc activity results from IG-MYC translocations. However, MYC aberrations are not limited to BLs and then have a negative prognostic impact. In this study, we investigated to which extent aberrant c-Myc activity plays a functional role in other aNHL and whether it is independent from MYC translocations. Based on a combined microarray analysis of human germinal center (GC) B cells transfected with c-Myc and 220 aNHLs cases, we developed a "c-Myc index." This index measures the extent to which lymphomas express c-Myc responsive genes. It comprises genes that are affected in a variety of tumors compared to normal tissue. This supports the view that aberrant c-Myc expression in GC B cells triggers a tumor-like expression pattern. As expected, the "c-Myc index" is very high in molecular Burkitt lymphoma (mBL), but more importantly also high within other aNHL. It constitutes a negative prognostic marker independent of established risk factors and of the presence of a MYC translocation. Our data provide new insights into the role of c-Myc activity in different lymphomas and raises the question of treatment changes for those patients under risk.
authors.affiliation: Department of Haematology and Oncology, University Medical Centre of the Georg-August University Göttingen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schrader
authors.forename: Stefan
authors.initials: S
authors.lastname: Bentink
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Michael
authors.initials: M
authors.lastname: Kuo
authors.forename: John R
authors.initials: JR
authors.lastname: Arrand
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Dieter
authors.initials: D
authors.lastname: Kube
authors.forename: Martina
authors.initials: M
authors.lastname: Vockerodt
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D016271:Proto-Oncogene Proteins c-myc