Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy

Hans Erik Johnsen, Kim Steve Bergkvist, Alexander Schmitz, Malene Krag Kjeldsen, Steen Møller Hansen, Michael Gaihede, Martin Agge Nørgaard, John Bæch, Marie-Louise Grønholdt, Frank Svendsen Jensen, Preben Johansen, Julie Støve Bødker, Martin Bøgsted, Karen Dybkær, for the Myeloma Stem Cell Network (Mscnet)

Publikation: Bidrag til tidsskriftReview (oversigtsartikel)peer review

15 Citationer (Scopus)


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.
TidsskriftLeukemia and Lymphoma
Udgave nummer6
Sider (fra-til)1251-1260
StatusUdgivet - 2014


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