TY - JOUR
T1 - Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy
AU - Johnsen, Hans Erik
AU - Bergkvist, Kim Steve
AU - Schmitz, Alexander
AU - Kjeldsen, Malene Krag
AU - Hansen, Steen Møller
AU - Gaihede, Michael
AU - Nørgaard, Martin Agge
AU - Bæch, John
AU - Grønholdt, Marie-Louise
AU - Jensen, Frank Svendsen
AU - Johansen, Preben
AU - Bødker, Julie Støve
AU - Bøgsted, Martin
AU - Dybkær, Karen
AU - for the Myeloma Stem Cell Network (Mscnet)
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.3109/10428194.2013.839785
DO - 10.3109/10428194.2013.839785
M3 - Review article
C2 - 23998255
SN - 1042-8194
VL - 55
SP - 1251
EP - 1260
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 6
ER -