Page 1386 - Hematology_ Basic Principles and Practice ( PDFDrive )

1232 Part VII Hematologic Malignancies

Ezh2 fl/fl Ezh2 Y641N Ezh2 Y641N
Vehicle Vehicle GSK503

PNA

500 µm

EZH2

Ki67

B220

Ezh2 fl/fl Ezh2 Y641N

H3K27me3 Ezh2 fl/fl

Ezh2 Y641N ∗∗
Histone 3
0 1 2 3
H3K27me3/H3
Fig. 76.2 EXPANSION OF GERMINAL CENTERS WITH EZH2 MUTATION CONFERRING
INCREASE HISTONE 3 LYSINE 36 TRIMETHYLATION (H3K36ME3). Upper color panels depict his-
tologic staining as indicated by row (PNA, EZH2, Ki67, B220) of murine mouse model bearing wild type
versus mutant (Y641N) EZH2 with or without exposure to EZH2 inhibitor GSK503. Panels at bottom depict
H3K36me3 levels according to EZH2 mutational status. (See Beguelin, W: EZH2 is required for germinal center
formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell 23: 677, 2013.)

Advances in molecular biology and genomic technologies have clari-
fied the basis for some of this observed heterogeneity, and it has GENE EXPRESSION PROFILES DEFINE DIFFUSE LARGE
become clear that DLBCL comprises a diverse group of lymphomas B-CELL LYMPHOMA SUBTYPES
that have distinct cellular origins, recurrent gene mutations, and
chromosomal rearrangements that dictate their behavior. It is also GEP has identified GC B cell–like (GCB) and activated B cell–like
clear that the stromal environment appears to play a key role in the (ABC) DLBCL subsets that express gene signatures that mimic
development and progression of DLBCL, as with other cancers. GCs and activated B cells (Fig. 76.3; Table 76.1). Roughly 30%