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Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2.

Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2.
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Horn H, Kohler C, Witzig R, Kreuz M, Leich E, Klapper W, Hummel M, Loeffler M, Trümper L, Spang R, Rosenwald A, Ott G,


Horn H, Kohler C, Witzig R, Kreuz M, Leich E, Klapper W, Hummel M, Loeffler M, Trümper L, Spang R, Rosenwald A, Ott G, (click to view)

Horn H, Kohler C, Witzig R, Kreuz M, Leich E, Klapper W, Hummel M, Loeffler M, Trümper L, Spang R, Rosenwald A, Ott G,

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Haematologica 2018 03 22() pii 10.3324/haematol.2017.181024

Abstract

A linear progression model of follicular lymphomas (FL) FL1, FL2 and FL3A has been favored, since FL 3A often coexist with a FL1/2 component. FL3B, in contrast, is thought to be more closely related to diffuse large B-cell lymphoma (DLBCL), and both FL3B and DLBCL are often simultaneously present in one tumor (DLBCL/FL3B). To obtain more detailed insights into FL progression, comprehensive analysis of a well-defined set of FL1/2 (n=22), FL3A (n=16), FL3B (n=6), DLBCL/FL3B (n=9) and germincal center B-cell(GCB)-type DLBCL (n=45) was performed using gene expression profiling, immunohistochemical staining and genetic analysis by fluorescence in situ hybridization (FISH). While immunohistochemical (CD10, IRF4/MUM1, Ki67, BCL2, BCL6) and genetic profiles (translocations of BCL2, BCL6 and MYC) delineate FL1-3A from FL3B and DLBCL/FL3B, significant differences were observed between FL1/2 and FL3A upon gene expression profiling (GEP). Interestingly, FL3B turned out to be closely related to FL3A, not categorizing within a separate GE cluster, and both FL3A and FL3B showed overlapping profiles in between FL1/2 and DLBCL. Finally, basing upon their gene expression pattern, DLBCL/FL3B represents a composite form of FL3B and DLBCL, with the majority of samples more closely resembling DLBCL. The fact that gene expression profiling clearly separated FL1/2 from both FL3A and FL3B suggests a closer biological relationship of the latter. This notion, however, stands in a certain contrast to immunohistochemical and genetic profiles of the different histologic FL subtypes that point to a closer relationship of FL1/2 and FL3A, and separating them from FL3B.

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