• Rituximab and autologous stem cell transplantation are both independently associated with improved overall survival in mantle cell lymphoma.• Male gender is an independent negative prognostic factor in mantle cell lymphoma.There is consensus that young patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens, but optimal treatment of elderly patients as well for as patients with limited or indolent disease is not defined. Our aim was to evaluate and compare outcome in relation to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000 to 2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased, most prominently among males. Furthermore, male gender was associated with inferior overall survival (OS) in multivariate analysis (hazard ratio [HR] 5 1.36; P 5 .002). Forty-three (3.6%) patients with stage I-II disease received radiotherapy with curative intent, showing a 3-year OS of 93%. Twenty-nine (2.4%) patients followed a watch-and-wait approach and showed a 3-year OS of 79.8%. Among patients receiving systemic treatment, rituximab (n 5 766; HR 5 0.66; P 5 .001) and autologous stem cell transplant (n 5 273; HR 5 0.55; P 5 .004) were independently associated with improved OS in multivariate analysis. Hence, by a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice. (Blood. 2014;124(8):1288-1295

SOX11 (Sex determining region Y-box 11) expression is specific for MCL as compared to other Non-Hodgkin's lymphomas. However, the function and direct binding targets of SOX11 in MCL are largely unknown. We used high-resolution ChIP-Seq to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11 target genes. qCHIP and promoter reporter assays confirmed that SOX11 directly binds to individual genes and modulates their transcription activities in these pathways in MCL. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolinska Institute and British Columbia Cancer Agency (BCCA). Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy. Transcriptional regulation of WNT and other biological pathways affected by SOX11 target genes may help explain the impact of SOX11 expression on patient outcomes.

Purpose: The purpose of this study was to investigate the impact of T-cell subsets on pathologic and clinical features including disease outcome in mantle cell lymphoma (MCL).Experimental Design: Cell populations were investigated using flow cytometry in diagnostic MCL (n ¼ 153) and reactive (n ¼ 26) lymph node biopsies. Levels of tumor cells, T cells, T-cell subsets, and the CD4:CD8 ratio were assessed and related to pathologic and clinical parameters.Results: MCL cases with diffuse and nodular histologic subtypes showed lower levels of T cells, especially CD4 þ T cells, than those with mantle zone growth pattern. Both CD3 and CD4 levels were lower in the nodular subtype than in mantle zone (P ¼ 0.007; P ¼ 0.003) and in the diffuse compared with the nodular subtype (P ¼ 0.022; P ¼ 0.015). The CD4:CD8 ratios were inversely correlated to tumor cell proliferation (P ¼ 0.003). Higher levels of CD3 þ and CD4 þ T cells and higher CD4:CD8 ratios were associated with indolent disease (P ¼ 0.043, 0.021, and 0.003 respectively). In univariate analysis, a high CD4:CD8 ratio, but not the histologic subtype, was correlated to longer overall survival (OS). In multivariate analysis, the CD4:CD8 ratio correlated with OS independently of Mantle Cell Lymphoma International Prognostic Index (MIPI) and high p53 expression (P ¼ 0.023).