Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Alizadeh, Ash A.; Gentles, Andrew J.; Alencar, Alvaro J.; Liu, Chih Long; Kohrt, Holbrook E.; Houot, Roch; Goldstein, Matthew; Song, Zhao; Natkunam, Yasodha; Advani, Ranjana H.; Gascoyne, Randy D.; Briones, Javier; Tibshirani, Robert; Myklebust, June Helen; Plevritis, Sylvia K.; Lossos, Izidore S.; Levy, Ronald

doi:10.1182/blood-2011-03-345272

Cited by 178 publications

(170 citation statements)

References 45 publications

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“…Our samples examined also did not include any neuronal tissue, so that the further investigation of the LMO3 expression is valuable for understanding its exact role in both normal and tumor cells. LMO2, also a member of the LMO family, is known as a biomarker of GCB DLBCL 30, 31. Several different characteristics for LMO2 and LMO3 have been described 25; however, our results of association with aggressive clinical features also suggest that LMO3 might have some relevant molecular mechanism in DLBCL cells, as LMO2 does.…”

Section: Discussionmentioning

confidence: 55%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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Diffuse large B‐cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5‐positive (CD5+) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5+ DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5,LMO3,SNAP25,SYT5,SV2C,CABP1,FGF1,FGFR2,NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B‐cell‐like DLBCL (P = 0.046). Compared to the SH3BP5‐negative group, the SH3BP5+ group was correlated with elderly onset (>60 years, P = 0.0096) and advanced‐stage disease (stage III/IV, P = 0.037). The LMO3+ group showed a worse performance status (>1, P = 0.0004). The SH3BP5+ group and the LMO3+ group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab‐containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL.

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Section: Discussionmentioning

confidence: 55%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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“…However, it is evident that the variables on which this index is constructed are partly surrogates for DLBCL biology [2], and that the IPIaa does not capture the full extent of the heterogeneity observed in this disease [30]. This is apparent as patients with an identical IPIaa score may exhibit a marked variability in OS, indicative of significant residual heterogeneity within each IPI category [6].…”

Section: Discussionmentioning

confidence: 99%

A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients

et al. 2016

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“…In the non-immunosuppressed, DLBCL biopsies display features of a host immune response, including genes and proteins associated with lymphocytes and monocytes [10][11][12][13]. In this respect, recent studies have demonstrated circulating immune cells measured by the complete blood counts (CBC), such as absolute lymphocyte counts (ALC) and absolute monocyte counts (AMC), either alone or in combination with each (e.g., lymphocyte/monocyte ratio: LMR), predict outcome independent of the R-IPI [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

Keane,

Gill,

Vari

et al. 2013

American J Hematol

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Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P 5 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD41 T-cell infiltration as the most significant predictor of outcome with 23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P 5 0.007) and OS (P 5 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD41 T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P 5 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP. Am. J.

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Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Cited by 178 publications

References 45 publications

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

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Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Cited by 178 publications

References 45 publications

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients

CD4+ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

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CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy