Abstract:
:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognized variability in clinical outcome, genetic features, and cells of origin. To date, transcriptional profiling has been used to highlight similarities between DLBCL tumor cells and normal B-cell subtypes and associate genes and pathways with unfavorable outcome. To identify robust and highly reproducible DL-BCL subtypes with comprehensive transcriptional signatures, we used a large series of newly diagnosed DLBCLs, whole genome arrays, and multiple clustering methods. Tumors were also analyzed for known common genetic abnormalities in DLBCL. There were 3 discrete subsets of DLBCL-"oxidative phosphorylation," "B-cell receptor/proliferation," and "host response" (HR)-identified characterized using gene set enrichment analysis and confirmed in an independent series. HR tumors had increased expression of T/natural killer cell receptor and activation pathway components, complement cascade members, macrophage/dendritic cell markers, and inflammatory mediators. HR DLB-CLs also contained significantly higher numbers of morphologically distinct CD2+/CD3+ tumor-infiltrating lymphocytes and interdigitating S100+/gamma interferon-induced lysosomal transferase-positive (GILT+) CD1a-/CD123- dendritic cells. The HR cluster shared features of histologically defined T-cell/histiocyte-rich B-cell lymphoma, including fewer genetic abnormalities, younger age at presentation, and frequent splenic and bone marrow involvement. These studies identify tumor microenvironment and host inflammatory response as defining features in DLBCL and suggest rational treatment targets in specific DLBCL subsets.
journal_name
Bloodjournal_title
Bloodauthors
Monti S,Savage KJ,Kutok JL,Feuerhake F,Kurtin P,Mihm M,Wu B,Pasqualucci L,Neuberg D,Aguiar RC,Dal Cin P,Ladd C,Pinkus GS,Salles G,Harris NL,Dalla-Favera R,Habermann TM,Aster JC,Golub TR,Shipp MAdoi
10.1182/blood-2004-07-2947subject
Has Abstractpub_date
2005-03-01 00:00:00pages
1851-61issue
5eissn
0006-4971issn
1528-0020pii
2004-07-2947journal_volume
105pub_type
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