Biomarkers of diffuse large B-cell lymphoma: impact on diagnosis, treatment, and prognosis

References

• Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–242.
   PubMed Web of Science ®Google Scholar
• Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23(22):5027–5033.
   PubMed Web of Science ®Google Scholar
• Pfreundschuh M, Trumper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379–391.
   PubMed Web of Science ®Google Scholar
• Pfreundschuh M, Schubert J, Ziepert M, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-6O). Lancet Oncol. 2008;9(2):105–116.
   PubMed Web of Science ®Google Scholar
• Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–2045.
   PubMed Web of Science ®Google Scholar
• Feugier P, Van Hoof A, Sebban C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23(18):4117–4126.
   PubMed Web of Science ®Google Scholar
• Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184–4190.
   PubMed Web of Science ®Google Scholar
• Larouche JF, Berger F, Chassagne-Clement C, et al. Lymphoma recurrence 5 years or later following diffuse large B-cell lymphoma: clinical characteristics and outcome. J Clin Oncol. 2010;28(12):2094–2100.
   PubMed Web of Science ®Google Scholar
• Shaknovich R, Geng H, Johnson NA, et al. DNA methylation signatures define molecular subtypes of diffuse large B-cell lymphoma. Blood. 2010;116(20):e81–e89.
   PubMed Web of Science ®Google Scholar
• Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: International Agency for Research on Cancer; 2008.
   Google Scholar
• Shaffer AL, Wright G, Yang L, et al. A library of gene expression signatures to illuminate normal and pathological lymphoid biology. Immunol Rev. 2006;210:67–85.
   PubMed Web of Science ®Google Scholar
• Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–511.
   PubMed Web of Science ®Google Scholar
• Lossos IS, Alizadeh AA, Eisen MB, et al. Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas. Proc Natl Acad Sci U S A. 2000;97(18):10209–10213.
   Web of Science ®Google Scholar
• Lenz G, Nagel I, Siebert R, et al. Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma. J Exp Med. 2007;204(3):633–643.
   PubMed Web of Science ®Google Scholar
• Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM. A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2003;100(17):9991–9996.
   PubMed Web of Science ®Google Scholar
• Lenz G, Wright GW, Emre NC, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A. 2008;105(36):13520–13525.
   PubMed Web of Science ®Google Scholar
• Pasqualucci L, Trifonov V, Fabbri G, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011;43(9):830–837.
   PubMed Web of Science ®Google Scholar
• Morin RD, Mendez-Lago M, Mungall AJ, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476(7360):298–303.
   PubMed Web of Science ®Google Scholar
• Lohr JG, Stojanov P, Lawrence MS, et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A. 2012;109(10):3879–3884.
   PubMed Web of Science ®Google Scholar
• Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937–1947.
   PubMed Web of Science ®Google Scholar
• Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359(22):2313–2323.
   PubMed Web of Science ®Google Scholar
• Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002;8(1):68–74.
   PubMed Web of Science ®Google Scholar
• Lossos IS, Czerwinski DK, Alizadeh AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med. 2004;350(18):1828–1837.
   PubMed Web of Science ®Google Scholar
• Malumbres R, Chen J, Tibshirani R, et al. Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP Blood. 2008;111(12):5509–5514.
   PubMed Web of Science ®Google Scholar
• Rimsza LM, Leblanc ML, Unger JM, et al. Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP, Blood. 2008;112(8):3425–3433.
   PubMed Web of Science ®Google Scholar
• Williams PM, Li R, Johnson NA, Wright G, Heath JD, Gascoyne RD. A novel method of amplification of FFPET-derived RNA enables accurate disease classification with microarrays. J Mol Diagn. 2010;12(5):680–686.
   PubMed Web of Science ®Google Scholar
• Rimsza LM, Wright G, Schwartz M, et al. Accurate classification of diffuse large B-cell lymphoma into germinal center and activated B-cell subtypes using a nuclease protection assay on formalin-fixed, paraffin-embedded tissues. Clin Cancer Res. 2011;17(11):3727–3732.
   PubMed Web of Science ®Google Scholar
• Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohis- tochemistry using a tissue microarray. Blood. 2004;103(1):275–282.
   PubMed Web of Science ®Google Scholar
• Choi WW, Weisenburger DD, Greiner TC, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15(17):5494–5502.
   PubMed Web of Science ®Google Scholar
• Meyer PN, Fu K, Greiner TC, et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol. 2011;29(2):200–207.
   PubMed Web of Science ®Google Scholar
• Visco C, Li Y, Xu-Monette ZY, et al. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Leukemia. 2012;26(9):2103–2113.
   PubMed Web of Science ®Google Scholar
• Dunleavy K, Pittaluga S, Czuczman MS, et al. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood. 2009;113(24):6069–6076.
   PubMed Web of Science ®Google Scholar
• Moskowitz CH, Zelenetz AD, Kewalramani T, et al. Cell of origin, germinal center versus nongerminal center, determined by immuno- histochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL. Blood. 2005;106(10):3383–3385.
   Web of Science ®Google Scholar
• Gutierrez-Garcia G, Cardesa-Salzmann T, Climent F, et al. Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood. 2011;117(18):4836–4843.
   PubMed Web of Science ®Google Scholar
• Fu K, Weisenburger DD, Choi WW, et al. Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol. 2008;26(28):4587–4594.
   PubMed Web of Science ®Google Scholar
• Vose JM. Relapsed diffuse large B-cell lymphoma: clinical utility of cell of origin. J Clin Oncol. 2011;29(31):4065–4066.
   Web of Science ®Google Scholar
• Bernd HW, Ziepert M, Thorns C, et al. Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma–analyses of cases from two prospective randomized clinical trials. Haematologica. 2009;94(11):1569–1580.
   PubMed Web of Science ®Google Scholar
• Chang CC, McClintock S, Cleveland RP, et al. Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma. Am J Surg Pathol. 2004;28(4):464–470.
   Web of Science ®Google Scholar
• Berglund M, Thunberg U, Amini RM, et al. Evaluation of immunophe- notype in diffuse large B-cell lymphoma and its impact on prognosis. ModPathol. 2005;18(8):1113–1120.
   Google Scholar
• Ott G, Ziepert M, Klapper W, et al. Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL. Blood. 2010;116(23):4916–4925.
   PubMed Web of Science ®Google Scholar
• De Paepe P, Achten R, Verhoef G, et al. Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas. J Clin Oncol. 2005;23(28):7060–7068.
   Web of Science ®Google Scholar
• Dupuis J, Gaulard P, Hemery F, et al. Respective prognostic values of germinal center phenotype and early (18) fluorodeoxyglucose-positron emission tomography scanning in previously untreated patients with diffuse large B-cell lymphoma. Haematologica. 2007;92(6):778–783.
   Web of Science ®Google Scholar
• Gu K, Weisenburger DD, Fu K, et al. Cell of origin fails to predict survival in patients with diffuse large B-cell lymphoma treated with autologous hematopoietic stem cell transplantation. Hematol Oncol. 2012;30(3):143–149.
   PubMed Web of Science ®Google Scholar
• Barrans SL, Carter I, Owen RG, et al. Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. Blood. 2002;99(4):1136–1143.
   PubMed Web of Science ®Google Scholar
• Curry CV Ewton AA, Olsen RJ, et al. Prognostic impact of C-REL expression in diffuse large B-cell lymphoma. J Hematop. 2009;2(1):20–26.
   Google Scholar
• Thieblemont C, Briere J, Mounier N, et al. The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol. 2011;29(31):4079–4087.
   PubMed Web of Science ®Google Scholar
• van Imhoff GW, Boerma EJ, van der Holt B, et al. Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(25):4135–4142.
   PubMed Web of Science ®Google Scholar
• de Jong D, Rosenwald A, Chhanabhai M, et al. Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications–a study from the Lunenburg Lymphoma Biomarker Consortium. J Clin Oncol. 2007;25(7):805–812.
   PubMed Web of Science ®Google Scholar
• A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329(14):987–994.
   PubMedGoogle Scholar
• Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP, Blood. 2007;109(5):1857–1861.
   PubMed Web of Science ®Google Scholar
• Salles G, de Jong D, Xie W, et al. Prognostic significance of immuno- histochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium. Blood. 2011;117(26):7070–7078.
   PubMed Web of Science ®Google Scholar
• Klapper W, Kreuz M, Kohler CW, et al. Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma. Blood. 2012;119(8):1882–1887.
   PubMed Web of Science ®Google Scholar
• Ngo L, Hee SW, Lim LC, et al. Prognostic factors in patients with diffuse large B cell lymphoma: Before and after the introduction of rituximab. Leuk Lymphoma. 2008;49(3):462–469.
   PubMed Web of Science ®Google Scholar
• Muller C, Murawski N, Wiesen MH, et al. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012;119(14):3276–3284.
   PubMed Web of Science ®Google Scholar
• Pfreundschuh M, Ho AD, Cavallin-Stahl E, et al. Prognostic significance of maximum tumour (bulk) diameter in young patients with good- prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol. 2008;9(5):435–444.
   PubMed Web of Science ®Google Scholar
• Gaudio F, Giordano A, Perrone T, et al. High Ki67 index and bulky disease remain significant adverse prognostic factors in patients with diffuse large B cell lymphoma before and after the introduction of rituximab. Acta Haematol. 2011;126(1):44–51.
   Web of Science ®Google Scholar
• Chung R, Lai R, Wei P, et al. Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index. Blood. 2007;110(4):1278–1282.
   PubMed Web of Science ®Google Scholar
• Sehn LH, Scott DW, Chhanabhai M, et al. Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2011;29(11):1452–1457.
   PubMed Web of Science ®Google Scholar
• Takahashi H, Tomita N, Yokoyama M, et al. Prognostic impact of extranodal involvement in diffuse large B-cell lymphoma in the rituximab era. Cancer. 2012;118(17):4166–4172.
   PubMed Web of Science ®Google Scholar
• Lopez-Guillermo A, Colomo L, Jimenez M, et al. Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin. J Clin Oncol. 2005 ;23(12):2797–2804.
   PubMed Web of Science ®Google Scholar
• Gutierrez-Garcia G, Colomo L, Villamor N, et al. Clinico-biological characterization and outcome of primary nodal and extranodal diffuse large B-cell lymphoma in the rituximab era. Leuk Lymphoma. 2010;51(7):1225–1232.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579–586.
   PubMed Web of Science ®Google Scholar
• Casasnovas RO, Meignan M, Berriolo-Riedinger A, et al. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood. 2011;118(1):37–43.
   PubMed Web of Science ®Google Scholar
• Safar V Dupuis J, Itti E, et al. Interim [18F] fluorodeoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy plus rituximab. J Clin Oncol. 2012;30(2):184–190.
   PubMed Web of Science ®Google Scholar
• Pregno P, Chiappella A, Bello M, et al. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP Blood. 2012;119(9):2066–2073.
   PubMed Web of Science ®Google Scholar
• Moskowitz CH, Schoder H, Teruya-Feldstein J, et al. Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in Advanced-stage diffuse large B-Cell lymphoma. J Clin Oncol. 2010;28(11):1896–1903.
   PubMed Web of Science ®Google Scholar
• Casasnovas RO, Meignan M, Berriolo-Riedinger A, et al. Early Interim PET Scans in Diffuse Large B-Cell lymphoma: can there be consensus about standardized reporting, and can PET scans guide therapy choices? Curr Hematol Malig Rep. 2012;7(3):193–199.
   PubMed Web of Science ®Google Scholar
• Horning SJ, Juweid ME, Schoder H, et al. Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. Blood. 2010;115(4):775–777; quiz 918.
   Web of Science ®Google Scholar
• Achten R, Verhoef G, Vanuytsel L, De Wolf-Peeters C. Histiocyte-rich, T-cell-rich B-cell lymphoma: a distinct diffuse large B-cell lymphoma subtype showing characteristic morphologic and immunophenotypic features. Histopathology. 2002;40(1):31–45.
   Web of Science ®Google Scholar
• Monti S, Savage KJ, Kutok JL, et al. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. 2005;105(5):1851–1861.
   Google Scholar
• Montes-Moreno S, Gonzalez-Medina AR, Rodriguez-Pinilla SM, et al. Aggressive large B-cell lymphoma with plasma cell differentiation: immunohistochemical characterization of plasmablastic lymphoma and diffuse large B-cell lymphoma with partial plasmablastic phenotype. Haematologica. 2010;95(8):1342–1349.
   Web of Science ®Google Scholar
• Kobayashi T, Yamaguchi M, Kim S, et al. Microarray reveals differences in both tumors and vascular specific gene expression in de novo CD5+ and CD5- diffuse large B-cell lymphomas. Cancer Res. 2003;63(1):60–66.
   Web of Science ®Google Scholar
• Tagawa H, Suguro M, Tsuzuki S, et al. Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma. Blood. 2005;106(5):1770–1777.
   PubMed Web of Science ®Google Scholar
• Ennishi D, Takeuchi K, Yokoyama M, et al. CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy. Ann Oncol. 2008;19(11):1921–1926.
   PubMed Web of Science ®Google Scholar
• Miyazaki K, Yamaguchi M, Suzuki R, et al. CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients treated by chemotherapy with or without rituximab. Ann Oncol. 2011;22(7):1601–1607.
   PubMed Web of Science ®Google Scholar
• Johnson NA, Boyle M, Bashashati A, et al. Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival. Blood. 2009;113(16):3773–3780.
   PubMed Web of Science ®Google Scholar
• Suzuki Y, Yoshida T, Wang G, et al. Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL. Ann Hematol. 2012;91(7):997–1005.
   Web of Science ®Google Scholar
• Ohshima K, Kawasaki C, Muta H, et al. CD10 and Bcl10 expression in diffuse large B-cell lymphoma: CD10 is a marker of improved prognosis. Histopathology. 2001;39(2):156–162.
   Web of Science ®Google Scholar
• Biasoli I, Morais JC, Scheliga A, et al. CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses. Histopathology. 2005;46(3):328–333.
   Web of Science ®Google Scholar
• Fabiani B, Delmer A, Lepage E, et al. CD10 expression in diffuse large B-cell lymphomas does not influence survival. Virchows Arch. 2004;445(6):545–551.
   Web of Science ®Google Scholar
• Muris JJ, Meijer CJ, Vos W, et al. Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. J Pathol. 2006;208(5):714–723.
   PubMed Web of Science ®Google Scholar
• Barrans SL, Fenton JA, Banham A, Owen RG, Jack AS. Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood. 2004;104(9):2933–2935.
   PubMed Web of Science ®Google Scholar
• Banham AH, Connors JM, Brown PJ, et al. Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin Cancer Res. 2005;11(3):1065–1072.
   PubMed Web of Science ®Google Scholar
• Hoeller S, Schneider A, Haralambieva E, Dirnhofer S, Tzankov A. FOXP1 protein overexpression is associated with inferior outcome in nodal diffuse large B-cell lymphomas with non-germinal centre phenotype, independent of gains and structural aberrations at 3p14.1. Histopathology. 2010;57(1):73–80.
   Web of Science ®Google Scholar
• Jiang X, Lu X, McNamara G, et al. HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway. Blood. 2010;116(24):5217–5227.
   Web of Science ®Google Scholar
• Lossos IS, Alizadeh AA, Rajapaksa R, Tibshirani R, Levy R. HGAL is a novel interleukin-4-inducible gene that strongly predicts survival in diffuse large B-cell lymphoma. Blood. 2003;101(2):433–440.
   Web of Science ®Google Scholar
• Natkunam Y, Lossos IS, Taidi B, et al. Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation. Blood. 2005;105(10):3979–3986.
   Web of Science ®Google Scholar
• Natkunam Y, Zhao S, Mason DY, et al. The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas. Blood. 2007;109(4):1636–1642.
   PubMed Web of Science ®Google Scholar
• Natkunam Y, Farinha P, Hsi ED, et al. LMO2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy with and without rituximab. J Clin Oncol. 2008;26(3):447–454.
   PubMed Web of Science ®Google Scholar
• Hans CP, Weisenburger DD, Greiner TC, et al. Expression of PKC- beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma. Mod Pathol. 2005;18(10):1377–1384.
   Web of Science ®Google Scholar
• Schaffel R, Morais JC, Biasoli I, et al. PKC-beta II expression has prognostic impact in nodal diffuse large B-cell lymphoma. Mod Pathol. 2007;20(3):326–330.
   Web of Science ®Google Scholar
• Espinosa I, Briones J, Bordes R, et al. Membrane PKC-beta 2 protein expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma. Ann Hematol. 2006;85(9):597–603.
   Web of Science ®Google Scholar
• Chaiwatanatorn K, Stamaratis G, Opeskin K, Firkin F, Nandurkar H. Protein kinase C-beta II expression in diffuse large B-cell lymphoma predicts for inferior outcome of anthracycline-based chemotherapy with and without rituximab. Leuk Lymphoma. 2009;50(10):1666–1675.
   PubMed Web of Science ®Google Scholar
• Chang CC, Liu YC, Cleveland RP, Perkins SL. Expression of c-Myc and p53 correlates with clinical outcome in diffuse large B-cell lymphomas. Am J Clin Pathol. 2000;113(4):512–518.
   Web of Science ®Google Scholar
• Hummel M, Bentink S, Berger H, et al. A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling. N Engl J Med. 2006;354(23):2419–2430.
   PubMed Web of Science ®Google Scholar
• Salaverria I, Siebert R. The gray zone between Burkitt’s lymphoma and diffuse large B-cell lymphoma from a genetics perspective. J Clin Oncol. 2011;29(14):1835–1843.
   PubMed Web of Science ®Google Scholar
• Klapper W, Stoecklein H, Zeynalova S, et al. Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL). Leukemia. 2008;22(12):2226–2229.
   PubMed Web of Science ®Google Scholar
• Savage KJ, Johnson NA, Ben-Neriah S, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009 ;114(17):3533–3537.
   PubMed Web of Science ®Google Scholar
• Johnson NA, Savage KJ, Ludkovski O, et al. Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival. Blood. 2009;114(11):2273–2279.
   PubMed Web of Science ®Google Scholar
• Obermann EC, Csato M, Dirnhofer S, Tzankov A. Aberrations of the MYC gene in unselected cases of diffuse large B-cell lymphoma are rare and unpredictable by morphological or immunohistochemical assessment. J Clin Pathol. 2009;62(8):754–756.
   PubMed Web of Science ®Google Scholar
• Barrans S, Crouch S, Smith A, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28(20):3360–3365.
   PubMed Web of Science ®Google Scholar
• Akyurek N, Uner A, Benekli M, Barista I. Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Cancer. 2012;118(17):4173–4183.
   PubMed Web of Science ®Google Scholar
• Cuccuini W, Briere J, Mounier N, et al. MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation. Blood. 2012;119(20):4619–4624.
   PubMed Web of Science ®Google Scholar
• Green TM, Nielsen O, de Stricker K, Xu-Monette ZY, Young KH, Moller MB. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am JSurg Pathol. 2012;36(4):612–619.
   Web of Science ®Google Scholar
• Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3452–3459.
   PubMed Web of Science ®Google Scholar
• Niitsu N, Okamoto M, Miura I, Hirano M. Clinical features and prognosis of de novo diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC translocations. Leukemia. 2009;23(4):777–783.
   PubMed Web of Science ®Google Scholar
• Green TM, Young KH, Visco C, et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-Cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3460–3467.
   PubMed Web of Science ®Google Scholar
• Barrans SL, Evans PA, O’Connor SJ, et al. The t(14;18) is associated with germinal center-derived diffuse large B-cell lymphoma and is a strong predictor of outcome. Clin Cancer Res. 2003;9(6):2133–2139.
   Web of Science ®Google Scholar
• Iqbal J, Sanger WG, Horsman DE, et al. BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. Am J Pathol. 2004;165(1):159–166.
   PubMed Web of Science ®Google Scholar
• Iqbal J, Meyer PN, Smith LM, et al. BCL2 predicts survival in germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab. Clin Cancer Res. 2011 ;17(24):7785–7795.
   PubMed Web of Science ®Google Scholar
• Schuetz JM, Johnson NA, Morin RD, et al. BCL2 mutations in diffuse large B-cell lymphoma. Leukemia. 2012;26(6):1383–1390.
   PubMed Web of Science ®Google Scholar
• Iqbal J, Neppalli VT, Wright G, et al. BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(6):961–968.
   PubMed Web of Science ®Google Scholar
• Obermann EC, Csato M, Dirnhofer S, Tzankov A. BCL2 gene aberration as an IPI-independent marker for poor outcome in non-germinal-centre diffuse large B cell lymphoma. J Clin Pathol. 2009;62(10):903–907.
   Web of Science ®Google Scholar
• Colomo L, Lopez-Guillermo A, Perales M, et al. Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. Blood. 2003;101(1):78–84.
   PubMed Web of Science ®Google Scholar
• Maeshima AM, Taniguchi H, Fukuhara S, et al. Bcl-2, Bcl-6, and the International Prognostic Index are prognostic indicators in patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy. Cancer Sci. 2012;103(10):1898–1904.
   Web of Science ®Google Scholar
• Mounier N, Briere J, Gisselbrecht C, et al. Rituximab plus CHOP (R-CHOP) overcomes bcl-2--associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood. 2003;101(11):4279–4284.
   PubMed Web of Science ®Google Scholar
• Wilson KS, Sehn LH, Berry B, et al. CHOP-R therapy overcomes the adverse prognostic influence of BCL-2 expression in diffuse large B-cell lymphoma. Leuk Lymphoma. 2007;48(6):1102–1109.
   PubMed Web of Science ®Google Scholar
• Iqbal J, Greiner TC, Patel K, et al. Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma. Leukemia. 2007;21(11):2332–2343.
   PubMed Web of Science ®Google Scholar
• Pasqualucci L, Migliazza A, Basso K, Houldsworth J, Chaganti RS, Dalla-Favera R. Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma. Blood. 2003;101(8):2914–2923.
   PubMed Web of Science ®Google Scholar
• Barrans SL, O’Connor SJ, Evans PA, et al. Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma. Br J Haematol. 2002;117(2):322–332.
   PubMed Web of Science ®Google Scholar
• Jerkeman M, Aman P, Cavallin-Stahl E, et al. Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma–a Nordic Lymphoma Group study. Int J Oncol. 2002;20(1):161–165.
   Web of Science ®Google Scholar
• Seki R, Ohshima K, Fujisaki T, et al. Prognostic impact of immuno- histochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. Cancer Sci. 2009;100(10):1842–1847.
   PubMed Web of Science ®Google Scholar
• Uccella S, Placidi C, Marchet S, et al. Bcl-6 protein expression, and not the germinal centre immunophenotype, predicts favourable prognosis in a series of primary nodal diffuse large B-cell lymphomas: a single centre experience. Leuk Lymphoma. 2008;49(7):1321–1328.
   PubMed Web of Science ®Google Scholar
• Winter JN, Weller EA, Horning SJ, et al. Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood. 2006;107(11):4207–4213.
   PubMed Web of Science ®Google Scholar
• Ichikawa A, Kinoshita T, Watanabe T, et al. Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma. N Engl J Med. 1997;337(8):529–534.
   PubMed Web of Science ®Google Scholar
• Wilson WH, Teruya-Feldstein J, Fest T, et al. Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin’s lymphomas. Blood. 1997;89(2):601–609.
   PubMed Web of Science ®Google Scholar
• Leroy K, Haioun C, Lepage E, et al. p53 gene mutations are associated with poor survival in low and low-intermediate risk diffuse large B-cell lymphomas. Ann Oncol. 2002;13(7):1108–1115.
   PubMed Web of Science ®Google Scholar
• Young KH, Weisenburger DD, Dave BJ, et al. Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma. Blood. 2007;110(13):4396–4405.
   PubMed Web of Science ®Google Scholar
• Young KH, Leroy K, Moller MB, et al. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood. 2008;112(8):3088–3098.
   PubMed Web of Science ®Google Scholar
• Zainuddin N, Berglund M, Wanders A, et al. TP53 mutations predict for poor survival in de novo diffuse large B-cell lymphoma of germinal center subtype. Leuk Res. 2009;33(1):60–66.
   PubMed Web of Science ®Google Scholar
• Stefancikova L, Moulis M, Fabian P, et al. Prognostic impact of p53 aberrations for R-CHOP-treated patients with diffuse large B-cell lymphoma. Int J Oncol. 2011;39(6):1413–1420.
   PubMed Web of Science ®Google Scholar
• Simonitsch-Klupp I, Hauser I, Ott G, et al. Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome. Leukemia. 2004;18(1):146–155.
   Web of Science ®Google Scholar
• Jardin F, Jais JP, Molina TJ, et al. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study. Blood. 2010;116(7):1092–1104.
   PubMed Web of Science ®Google Scholar
• Salaverria I, Philipp C, Oschlies I, et al. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood. 2011;118(1):139–147.
   PubMed Web of Science ®Google Scholar
• Scott DW, Mungall KL, Ben-Neriah S, et al. TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma. Blood. 2012;119(21):4949–4952.
   PubMed Web of Science ®Google Scholar
• Alencar AJ, Malumbres R, Kozloski GA, et al. MicroRNAs are independent predictors of outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Clin Cancer Res. 2011;17(12) :4125–4135.
   PubMed Web of Science ®Google Scholar
• Montes-Moreno S, Martinez N, Sanchez-Espiridion B, et al. MicroRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy. Blood. 2011;118(4):1034–1040.
   Web of Science ®Google Scholar
• Markovic O, Marisavljevic D, Cemerikic V et al. Clinical and prognostic significance of apoptotic profile in patients with newly diagnosed nodal diffuse large B-cell lymphoma (DLBCL). Eur J Haematol. 2011;86(3):246–255.
   Web of Science ®Google Scholar
• Mainou-Fowler T, Overman LM, Dignum H, et al. A new subtype- specific monoclonal antibody for IAP-survivin identifies high-risk patients with diffuse large B-cell lymphoma and improves the prognostic value of bcl-2. Int J Oncol. 2008;32(1):59–68.
   Web of Science ®Google Scholar
• Hussain AR, Uddin S, Ahmed M, et al. Prognostic significance of XIAP expression in DLBCL and effect of its inhibition on AKT signalling. J Pathol. 2010;222(2):180–190.
   PubMed Web of Science ®Google Scholar
• Muris JJ, Ylstra B, Cillessen SA, et al. Profiling of apoptosis genes allows for clinical stratification of primary nodal diffuse large B-cell lymphomas. Br J Haematol. 2007;136(1):38–47.
   PubMed Web of Science ®Google Scholar
• Saez AI, Saez AJ, Artiga MJ, et al. Building an outcome predictor model for diffuse large B-cell lymphoma. Am J Pathol. 2004;164(2):613–622.
   Web of Science ®Google Scholar
• Tzankov A, Gschwendtner A, Augustin F, et al. Diffuse large B-cell lymphoma with overexpression of cyclin e substantiates poor standard treatment response and inferior outcome. Clin Cancer Res. 2006;12(7 Pt 1):2125–2132.
   Web of Science ®Google Scholar
• Winter JN, Li S, Aurora V et al. Expression of p21 protein predicts clinical outcome in DLBCL patients older than 60 years treated with R-CHOP but not CHOP: a prospective ECOG and Southwest Oncology Group correlative study on E4494. Clin Cancer Res. 2010;16(8):2435–2442.
   Web of Science ®Google Scholar
• Guney S, Jardin F, Bertrand P, et al. Several mechanisms lead to the inactivation of the CDKN2A (P16), P14 ARF, or CDKN2B (P15) genes in the GCB and ABC molecular DLBCL subtypes. Genes Chromosomes Cancer. 2012;51(9):858–867.
   Web of Science ®Google Scholar
• Sakane-Ishikawa E, Nakatsuka S, Tomita Y, et al. Prognostic significance of BACH2 expression in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group. J Clin Oncol. 2005;23(31):8012–8017.
   Web of Science ®Google Scholar
• Jang KY, Hwang SH, Kwon KS, et al. SIRT1 expression is associated with poor prognosis of diffuse large B-cell lymphoma. Am J Surg Pathol. 2008;32(10):1523–1531.
   PubMed Web of Science ®Google Scholar
• van Galen JC, Muris JJ, Oudejans JJ, et al. Expression of the polycomb- group gene BMI1 is related to an unfavourable prognosis in primary nodal DLBCL. J Clin Pathol. 2007;60(2):167–172.
   PubMed Web of Science ®Google Scholar
• Maurer MJ, Micallef IN, Cerhan JR, et al. Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma. J Clin Oncol. 2011;29(12):1620–1626.
   PubMed Web of Science ®Google Scholar
• Andreadis C, Gimotty PA, Wahl P, et al. Members of the glutathione and ABC-transporter families are associated with clinical outcome in patients with diffuse large B-cell lymphoma. Blood. 2007;109(8):3409–3416.
   Web of Science ®Google Scholar
• Tome ME, Johnson DB, Rimsza LM, et al. A redox signature score identifies diffuse large B-cell lymphoma patients with a poor prognosis. Blood. 2005;106(10):3594–3601.
   Web of Science ®Google Scholar
• Linderoth J, Eden P, Ehinger M, et al. Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma. Br J Haematol. 2008;141(4):423–432.
   Web of Science ®Google Scholar
• Jais JP, Haioun C, Molina TJ, et al. The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab. Leukemia. 2008;22(10):1917–1924.
   Web of Science ®Google Scholar
• Alizadeh AA, Gentles AJ, Alencar AJ, et al. Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood. 2011;118(5):1350–1358.
   PubMed Web of Science ®Google Scholar
• Kohrt HE, Houot R, Goldstein MJ, et al. CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies. Blood. 2011;117(8):2423–2432.
   PubMed Web of Science ®Google Scholar
• Habermann TM, Wang SS, Maurer MJ, et al. Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era. Blood. 2008;112(7):2694–2702.
   PubMed Web of Science ®Google Scholar
• Lech-Maranda E, Baseggio L, Charlot C, et al. Genetic polymorphisms in the proximal IL-10 promoter and susceptibility to non-Hodgkin lymphoma. Leuk Lymphoma. 2007;48(11):2235–2238.
   PubMed Web of Science ®Google Scholar
• Berglund M, Thunberg U, Roos G, Rosenquist R, Enblad G. The interleukin-10 gene promoter polymorphism (-1082) does not correlate with clinical outcome in diffuse large B-cell lymphoma. 2005;105(12):4894–4895; author reply 4895.
   Google Scholar
• Kim MK, Suh C, Chi HS, et al. VEGFA and VEGFR2 genetic polymorphisms and survival in patients with diffuse large B cell lymphoma. Cancer Sci. 2012;103(3):497–503.
   Web of Science ®Google Scholar
• Schoof N, von Bonin F, Zeynalova S, et al. Favorable impact of the interleukin-4 receptor allelic variant I75 on the survival of diffuse large B-cell lymphoma patients demonstrated in a large prospective clinical trial. Ann Oncol. 2009;20(9):1548–1554.
   Web of Science ®Google Scholar
• Chae YS, Kim JG, Sohn SK, et al. Lymphotoxin alfa and receptor- interacting protein kinase 1 gene polymorphisms may correlate with prognosis in patients with diffuse large B cell lymphoma treated with R-CHOP Cancer Chemother Pharmacol 2010;65(3):571–577.
   Google Scholar
• Miller TP, Lippman SM, Spier CM, Slymen DJ, Grogan TM. HLA-DR (Ia) immune phenotype predicts outcome for patients with diffuse large cell lymphoma. J Clin Invest. 1988;82(1):370–372.
   Web of Science ®Google Scholar
• Chang KC, Huang GC, Jones D, Lin YH. Distribution patterns of dendritic cells and T cells in diffuse large B-cell lymphomas correlate with prognoses. Clin Cancer Res. 2007;13(22 Pt 1):6666–6672.
   PubMed Web of Science ®Google Scholar
• Rimsza LM, Roberts RA, Miller TP, et al. Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood. 2004;103(11):4251–4258.
   PubMed Web of Science ®Google Scholar
• Stopeck AT, Gessner A, Miller TP, et al. Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma. Clin Cancer Res. 2000;6(10):3904–3909.
   Web of Science ®Google Scholar
• Challa-Malladi M, Lieu YK, Califano O, et al. Combined genetic inactivation of beta2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell. 2011;20(6):728–740.
   PubMed Web of Science ®Google Scholar
• Lech-Maranda E, Bienvenu J, Michallet AS, et al. Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B-cell lymphoma. Eur Cytokine Netw. 2006;17(1):60–66.
   Web of Science ®Google Scholar
• Lech-Maranda E, Bienvenu J, Broussais-Guillaumot F, et al. Plasma TNF-alpha and IL-10 level-based prognostic model predicts outcome of patients with diffuse large B-Cell lymphoma in different risk groups defined by the International Prognostic Index. Arch Immunol Ther Exp (Warsz). 2010;58(2):131–141.
   Web of Science ®Google Scholar
• Goto N, Tsurumi H, Kasahara S, et al. Serum interleukin-18 level is associated with the outcome of patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP regimens. Eur J Haematol. 2011;87(3):217–227.
   PubMed Web of Science ®Google Scholar
• Ennishi D, Yokoyama M, Terui Y, et al. Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy. Ann Oncol. 2009;20(3):526–533.
   Web of Science ®Google Scholar
• Goto N, T surumi H, Goto H, et al. Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens. Ann Hematol. 2012;91(5):705–714.
   PubMed Web of Science ®Google Scholar
• Cox MC, Nofroni I, Laverde G, et al. Absolute lymphocyte count is a prognostic factor in diffuse large B-cell lymphoma. Br J Haematol. 2008;141(2):265–268.
   Web of Science ®Google Scholar
• Feng J, Wang Z, Guo X, Chen Y, Cheng Y, Tang Y. Prognostic significance of absolute lymphocyte count at diagnosis of diffuse large B-cell lymphoma: a meta-analysis. Int J Hematol. 2012;95(2):143–148.
   PubMed Web of Science ®Google Scholar
• Plonquet A, Haioun C, Jais JP, et al. Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2–3 diffuse large B-cell lymphoma. Ann Oncol. 2007;18(7):1209–1215.
   Web of Science ®Google Scholar
• Porrata LF, Ristow K, Habermann TM, et al. Absolute monocyte/ lymphocyte count prognostic score is independent of immunohis- tochemically determined cell of origin in predicting survival in diffuse large B-cell lymphoma. LeukLymphoma. 2012;53(11):2159–2165.
   PubMed Web of Science ®Google Scholar
• Wilcox RA, Ristow K, Habermann TM, et al. The absolute monocyte and lymphocyte prognostic score predicts survival and identifies highrisk patients in diffuse large-B-cell lymphoma. Leukemia. 2011 ;25(9):1502–1509.
   PubMed Web of Science ®Google Scholar
• Tadmor T, Fell R, Polliack A, Attias D. Absolute monocytosis at diagnosis correlates with survival in diffuse large B-cell lymphoma- possible link with monocytic myeloid-derived suppressor cells. Hematol Oncol. Epub June 20, 2012.
   Google Scholar
• Mittal S, Marshall NA, Duncan L, Culligan DJ, Barker RN, Vickers MA. Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma. Blood. 2008;111(11):5359–5370.
   Web of Science ®Google Scholar
• Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32(5):593–604.
   PubMed Web of Science ®Google Scholar
• Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177(10):7303–7311.
   PubMed Web of Science ®Google Scholar
• Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5(12):953–964.
   PubMed Web of Science ®Google Scholar
• Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8(8):618–631.
   PubMed Web of Science ®Google Scholar
• Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–444.
   PubMed Web of Science ®Google Scholar
• Ojalvo LS, King W, Cox D, Pollard JW. High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am J Pathol. 2009;174(3):1048–1064.
   PubMed Web of Science ®Google Scholar
• Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–555.
   PubMed Web of Science ®Google Scholar
• Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 1999;17:593–623.
   PubMed Web of Science ®Google Scholar
• Becker S, Daniel EG. Antagonistic and additive effects of IL-4 and interferon-gamma on human monocytes and macrophages: effects on Fc receptors, HLA-D antigens, and superoxide production. Cell Immunol. 1990;129(2):351–362.
   Web of Science ®Google Scholar
• Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med. 1992;176(1):287–292.
   PubMed Web of Science ®Google Scholar
• Sinha P, Clements VK, Miller S, Ostrand-Rosenberg S. Tumor immunity: a balancing act between T cell activation, macrophage activation and tumor-induced immune suppression. Cancer Immunol Immunother. 2005;54(11):1137–1142.
   PubMed Web of Science ®Google Scholar
• Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol. 2010;10(8):554–567.
   PubMed Web of Science ®Google Scholar
• Sica A, Saccani A, Bottazzi B, et al. Autocrine production of IL-10 mediates defective IL-12 production and NF-kappa B activation in tumor-associated macrophages. J Immunol. 2000;164(2):762–767.
   PubMed Web of Science ®Google Scholar
• Wong SC, Puaux AL, Chittezhath M, et al. Macrophage polarization to a unique phenotype driven by B cells. Eur J Immunol. 2010;40(8):2296–2307.
   Web of Science ®Google Scholar
• Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677–686.
   PubMed Web of Science ®Google Scholar
• Martinez FO, Sica A, Mantovani A, Locati M. Macrophage activation and polarization. Front Biosci. 2008;13:453–461.
   PubMed Web of Science ®Google Scholar
• Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889–896.
   PubMed Web of Science ®Google Scholar
• Vacca A, Ribatti D, Ruco L, et al. Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Br J Cancer. 1999;79(5–6):965–970.
   Web of Science ®Google Scholar
• Hasselblom S, Hansson U, Sigurdardottir M, Nilsson-Ehle H, Ridell B, Andersson PO. Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosis. Pathol Int. 2008;58(8):529–532.
   Web of Science ®Google Scholar
• Cai QC, Liao H, Lin SX, et al. High expression of tumor-infiltrating macrophages correlates with poor prognosis in patients with diffuse large B-cell lymphoma. Med Oncol. 2012;29(4):2317–2322.
   Web of Science ®Google Scholar
• Wada N, Zaki MA, Hori Y, et al. Tumour-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group. Histopathology. 2012;60(2):313–319.
   PubMed Web of Science ®Google Scholar
• Ruan J, Hyjek E, Kermani P, et al. Magnitude of stromal hemangiogen- esis correlates with histologic subtype of non-Hodgkin’s lymphoma. Clin Cancer Res. 2006;12(19):5622–5631.
   Web of Science ®Google Scholar
• Tzankov A, Heiss S, Ebner S, et al. Angiogenesis in nodal B cell lymphomas: a high throughput study. J Clin Pathol. 2007;60(5):476–482.
   Web of Science ®Google Scholar
• Gratzinger D, Zhao S, Marinelli RJ, et al. Microvessel density and expression of vascular endothelial growth factor and its receptors in diffuse large B-cell lymphoma subtypes. Am J Pathol. 2007;170(4):1362–1369.
   PubMed Web of Science ®Google Scholar
• Cardesa-Salzmann TM, Colomo L, Gutierrez G, et al. High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. Haematologica. 2011;96(7):996–1001.
   PubMed Web of Science ®Google Scholar
• Evens AM, Sehn LH, Farinha P, et al. Hypoxia-inducible factor-1 {alpha} expression predicts superior survival in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2010;28(6):1017–1024.
   Web of Science ®Google Scholar
• Meyer PN, Fu K, Greiner T, et al. The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab. Am J Clin Pathol 2011;135(1):54–61.
   Web of Science ®Google Scholar
• Perry AM, Cardesa-Salzmann TM, Meyer PN, et al. A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma. Blood. 2012;120(11):2290–2296.
   PubMed Web of Science ®Google Scholar
• Muris JJ, Meijer CJ, Cillessen SA, et al. Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas. Leukemia. 2004;18(3):589–596.
   Web of Science ®Google Scholar
• Hasselblom S, Sigurdadottir M, Hansson U, Nilsson-Ehle H, Ridell B, Andersson PO. The number of tumour-infiltrating TIA-1+ cytotoxic T cells but not FOXP3+ regulatory T cells predicts outcome in diffuse large B-cell lymphoma. Br J Haematol. 2007;137(4):364–373.
   PubMed Web of Science ®Google Scholar
• Tzankov A, Meier C, Hirschmann P, Went P, Pileri SA, Dirnhofer S. Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma. Haematologica. 2008;93(2):193–200.
   PubMed Web of Science ®Google Scholar
• Saez AI, Garcia-Cosio M, Saez AJ, et al. Identification of biological markers of sensitivity to high-clinical-risk-adapted therapy for patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2009;50(4):571–581.
   PubMed Web of Science ®Google Scholar
• Lee NR, Song EK, Jang KY, et al. Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis. Leuk Lymphoma. 2008;49(2):247–256.
   PubMed Web of Science ®Google Scholar
• Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, Timmerman JM. Programmed death ligand 1 is expressed by non- hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011;17(13):4232–4244.
   PubMed Web of Science ®Google Scholar
• Hedstrom G, Berglund M, Molin D, et al. Mast cell infiltration is a favourable prognostic factor in diffuse large B-cell lymphoma. Br J Haematol. 2007;138(1):68–71.
   Web of Science ®Google Scholar
• Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002;99(3):754–758.
   PubMed Web of Science ®Google Scholar
• Mossner E, Brunker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010;115(22):4393–4402.
   PubMed Web of Science ®Google Scholar
• Lim SH, Vaughan AT, Ashton-Key M, et al. Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy. Blood. 2011;118(9):2530–2540.
   PubMed Web of Science ®Google Scholar
• Beers SA, French RR, Chan HT, et al. Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection. Blood. 2010;115(25):5191–5201.
   PubMed Web of Science ®Google Scholar
• Yang Y, Shaffer AL 3rd, Emre NC, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21(6):723–737.
   PubMed Web of Science ®Google Scholar
• Ruan J, Martin P, Furman RR, et al. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011;29(6):690–697.
   PubMed Web of Science ®Google Scholar
• Ribrag V, Gisselbrecht C, Haioun C, et al. Efficacy and toxicity of 2 schedules of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone plus bortezomib in patients with B-cell lymphoma: a randomized Phase 2 trial from the French Adult Lymphoma Study Group (GELA). Cancer. 2009;115(19):4540–4546.
   PubMed Web of Science ®Google Scholar
• Davis RE, Ngo VN, Lenz G, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010;463(7277):88–92.
   PubMed Web of Science ®Google Scholar
• Chen L, Monti S, Juszczynski P, et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood. 2008;111(4):2230–2237.
   PubMed Web of Science ®Google Scholar
• Cheng S, Coffey G, Zhang XH, et al. SYK inhibition and response prediction in diffuse large B-cell lymphoma. Blood. 2011;118(24):6342–6352.
   PubMed Web of Science ®Google Scholar
• Naylor TL, Tang H, Ratsch BA, et al. Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas. Cancer Res. 2011;71(7):2643–2653.
   PubMed Web of Science ®Google Scholar
• Kloo B, Nagel D, Pfeifer M, et al. Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells. Proc Natl Acad Sci U S A. 2011;108(1):272–277.
   PubMed Web of Science ®Google Scholar
• Friedberg JW, Sharman J, Sweetenham J, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115(13):2578–2585.
   PubMed Web of Science ®Google Scholar
• Robertson MJ, Kahl BS, Vose JM, et al. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2007;25(13):1741–1746.
   PubMed Web of Science ®Google Scholar
• Gupta M, Han JJ, Stenson M, et al. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. Blood. 2012;119(12):2844–2853.
   PubMed Web of Science ®Google Scholar
• Gupta M, Han JJ, Stenson M, Wellik L, Witzig TE. Regulation of STAT3 by histone deacetylase-3 in diffuse large B-cell lymphoma: implications for therapy. Leukemia. 2012;26(6):1356–1364.
   PubMed Web of Science ®Google Scholar
• Liu Y, Deng J, Wang L, et al. S1PR1 is an effective target to block STAT3 signaling in activated B cell-like diffuse large B-cell lymphoma. Blood. 2012;120(7):1458–1465.
   PubMed Web of Science ®Google Scholar
• Pro B, Leber B, Smith M, et al. Phase II multicenter study of oblim- ersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma. Br J Haematol. 2008;143(3):355–360.
   PubMed Web of Science ®Google Scholar
• Juszczynski P Chen L, O’Donnell E, et al. BCL6 modulates tonic BCR signaling in diffuse large B-cell lymphomas by repressing the SYK phosphatase, PTPROt. Blood. 2009;114(26):5315–5321.
   PubMed Web of Science ®Google Scholar
• Cerchietti LC, Polo JM, Da Silva GF, et al. Sequential transcription factor targeting for diffuse large B-cell lymphomas. Cancer Res. 2008;68(9):3361–3369.
   Web of Science ®Google Scholar
• Shaffer AL 3rd, Young RM, Staudt LM. Pathogenesis of human B cell lymphomas. Annu Rev Immunol. 2012;30:565–610.
   PubMed Web of Science ®Google Scholar
• Galustian C, Meyer B, Labarthe MC, et al. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother. 2009;58(7):1033–1045.
   PubMed Web of Science ®Google Scholar
• Ramsay AG, Clear AJ, Kelly G, et al. Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy. Blood. 2009;114(21):4713–4720.
   PubMed Web of Science ®Google Scholar
• Wu L, Adams M, Carter T, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res. 2008;14(14):4650–4657.
   PubMed Web of Science ®Google Scholar
• Breitkreutz I, Raab MS, Vallet S, et al. Lenalidomide inhibits osteoclas- togenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia. 2008;22(10):1925–1932.
   PubMed Web of Science ®Google Scholar
• Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26(30):4952–4957.
   PubMed Web of Science ®Google Scholar
• Witzig TE, Vose JM, Zinzani PL, et al. An international Phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol. 2011;22(7):1622–1627.
   PubMed Web of Science ®Google Scholar
• Zinzani PL, Pellegrini C, Gandolfi L, et al. Combination of lenalido- mide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a Phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011;11(6):462–466.
   PubMed Web of Science ®Google Scholar
• Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, et al. Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer. 2011;117(22):5058–5066.
   PubMed Web of Science ®Google Scholar
• Singh RR, Kim JE, Davuluri Y, et al. Hedgehog signaling pathway is activated in diffuse large B-cell lymphoma and contributes to tumor cell survival and proliferation. Leukemia. 2010;24(5):1025–1036.
   Web of Science ®Google Scholar
• Singh RR, Kunkalla K, Qu C, et al. ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma. Oncogene. 2011;30(49):4874–4886.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Bartlett NL, Vose JM, et al. A Phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B-cell lymphoma. Cancer. 2012;118(12):3128–3134.
   PubMed Web of Science ®Google Scholar
• Gomez-Abad C, Pisonero H, Blanco-Aparicio C, et al. PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma. Blood. 2011;118(20):5517–5527.
   PubMed Web of Science ®Google Scholar