PT  - JOURNAL ARTICLE
AU  - Kohta Miyawaki
AU  - Koji Kato
AU  - Takeshi Sugio
AU  - Kensuke Sasaki
AU  - Hiroaki Miyoshi
AU  - Yuichiro Semba
AU  - Yoshikane Kikushige
AU  - Yasuo Mori
AU  - Yuya Kunisaki
AU  - Hiromi Iwasaki
AU  - Toshihiro Miyamoto
AU  - Frank C. Kuo
AU  - Jon C. Aster
AU  - Koichi Ohshima
AU  - Takahiro Maeda
AU  - Koichi Akashi
TI  - A Germinal Center-Associated Microenvironmental Signature Reflects Malignant Phenotype and Outcome of Diffuse Large B-cell Lymphoma
AID  - 10.1101/833947
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 833947
4099  - http://biorxiv.org/content/early/2019/11/07/833947.short
4100  - http://biorxiv.org/content/early/2019/11/07/833947.full
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy with varying prognosis after the gold standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Several prognostic models have been established by focusing primarily on characteristics of lymphoma cells themselves including cell-of-origin, genomic alterations, and gene/protein expressions. However, the prognostic impact of lymphoma microenvironment and its association with characteristics of lymphoma cells are not fully understood. Using highly-sensitive transcriptome profiling of untreated DLBCL tissues, we here assess the clinical impact of lymphoma microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL. The presence of normal germinal center (GC)-microenvironmental cells, including follicular T cells, macrophage/dendritic cells, and stromal cells, in lymphoma tissue indicates a positive therapeutic response. Our prognostic model, based on quantitation of transcripts from distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis independently of existing prognostic models. We observed increased incidences of genomic alterations and aberrant gene expression associated with poor prognosis in DLBCL tissues lacking GC-microenvironmental cells relative to those containing these cells. These data suggest that the loss of GC-associated microenvironmental signature dictates clinical outcomes of DLBCL patients reflecting the accumulation of “unfavorable” molecular signatures.