title: Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy.
abstract: Recent findings have suggested biological classification of B-cell malignancies as exemplified by the "activated B-cell-like" (ABC), the "germinal-center B-cell-like" (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and "recurrent translocation and cyclin D" (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.
authors.affiliation: Department of Hematology and Aalborg Hospital Science and Innovation Center (AHSIC).
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Johnsen
authors.forename: Kim Steve
authors.initials: KS
authors.lastname: Bergkvist
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmitz
authors.forename: Malene Krag
authors.initials: MK
authors.lastname: Kjeldsen
authors.forename: Steen Møller
authors.initials: SM
authors.lastname: Hansen
authors.forename: Michael
authors.initials: M
authors.lastname: Gaihede
authors.forename: Martin Agge
authors.initials: MA
authors.lastname: Nørgaard
authors.forename: John
authors.initials: J
authors.lastname: Bæch
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Grønholdt
authors.forename: Frank Svendsen
authors.initials: FS
authors.lastname: Jensen
authors.forename: Preben
authors.initials: P
authors.lastname: Johansen
authors.forename: Julie Støve
authors.initials: JS
authors.lastname: Bødker
authors.forename: Martin
authors.initials: M
authors.lastname: Bøgsted
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkær
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D015448:Leukemia, B-Cell / Q000175:diagnosis* / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods; D015233:Models, Statistical; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics; D059467:Transcriptome
keywords: Flow cytometry; cancer; cell of origin; cell sorting; gene expression profiling