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Molecular Pathogenesis of Aggressive B-cell Lymphomas

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Molecular Aspects of Hematologic Malignancies

Part of the book series: Principles and Practice ((PRINCIPLES))

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Abstract

B-cell lymphomas are tumors arising from B-lymphoid cells at different stages of their development. In this chapter, we discuss the molecular pathogenesis of these tumors, specifically highlighting processes generating functional immunoglobulin genes that are associated with increased risk of genetic errors leading to lymphomagenesis. We review and summarize the enormous progress in understanding the pathologic, molecular, and clinical heterogeneity of these tumors that has been made during the past decades with the aid of high-throughput, platform-based gene expression, and associated functional studies. Finally, we discuss the translational consequences of these studies and review the emerging therapeutic strategies in aggressive lymphomas.

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References

  • Abramson JS, Shipp MA (2005) Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach. Blood 106(4):1164–1174

    Article  PubMed  CAS  Google Scholar 

  • Adams J (2004) The proteasome: a suitable antineoplastic target. Nat Rev Cancer 4(5):349–360

    Article  PubMed  CAS  Google Scholar 

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403(6769):503–511

    Article  PubMed  CAS  Google Scholar 

  • Bidere N, Ngo VN, Lee J, Collins C, Zheng L, Wan F, Davis RE, Lenz G, Anderson DE, Arnoult D, Vazquez A, Sakai K, Zhang J, Meng Z, Veenstra TD, Staudt LM, Lenardo MJ (2009) Casein kinase 1alpha governs antigen-receptor-induced NF-kappaB activation and human lymphoma cell survival. Nature 458(7234):92–96

    Article  PubMed  CAS  Google Scholar 

  • Bross L, Fukita Y, McBlane F, Demolliere C, Rajewsky K, Jacobs H (2000) DNA double-strand breaks in immunoglobulin genes undergoing somatic hypermutation. Immunity 13(5):589–597

    Article  PubMed  CAS  Google Scholar 

  • Busslinger M (2004) Transcriptional control of early B cell development. Annu Rev Immunol 22:55–79

    Article  PubMed  CAS  Google Scholar 

  • Cerchietti LC, Ghetu AF, Zhu X, Da Silva GF, Zhong S, Matthews M, Bunting KL, Polo JM, Fares C, Arrowsmith CH, Yang SN, Garcia M, Coop A, Mackerell AD Jr, Prive GG, Melnick A (2010) A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell 17(4):400–411

    Article  PubMed  CAS  Google Scholar 

  • Cerchietti LC, Yang SN, Shaknovich R, Hatzi K, Polo JM, Chadburn A, Dowdy SF, Melnick A (2009) A peptomimetic inhibitor of BCL6 with potent antilymphoma effects in vitro and in vivo. Blood 113(15):3397–3405

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Monti S, Juszczynski P, Daley J, Chen W, Witzig TE, Habermann TM, Kutok JL, Shipp MA (2008) SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 111(4):2230–2237

    Article  PubMed  CAS  Google Scholar 

  • Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, Braziel RM, Geng H, Iqbal J, Lenz G, Vose JM, Hans CP, Fu K, Smith LM, Li M, Liu Z, Gascoyne RD, Rosenwald A, Ott G, Rimsza LM, Campo E, Jaffe ES, Jaye DL, Staudt LM, Chan WC (2009) A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res 15(17):5494–5502

    Article  PubMed  CAS  Google Scholar 

  • Ci W, Polo JM, Cerchietti L, Shaknovich R, Wang L, Yang SN, Ye K, Farinha P, Horsman DE, Gascoyne RD, Elemento O, Melnick A (2009) The BCL6 transcriptional program features repression of multiple oncogenes in primary B cells and is deregulated in DLBCL. Blood 113(22):5536–5548

    Article  PubMed  CAS  Google Scholar 

  • Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, Bertoni F, Ponzoni M, Scandurra M, Califano A, Bhagat G, Chadburn A, Dalla-Favera R, Pasqualucci L (2009) Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 459(7247):717–721

    Article  PubMed  CAS  Google Scholar 

  • Dal Porto JM, Gauld SB, Merrell KT, Mills D, Pugh-Bernard AE, Cambier J (2004) B cell antigen receptor signaling 101. Mol Immunol 41(6–7):599–613

    Article  PubMed  CAS  Google Scholar 

  • Davis RE, Brown KD, Siebenlist U, Staudt LM (2001) Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 194(12):1861–1874

    Article  PubMed  CAS  Google Scholar 

  • Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, Xu W, Shaffer AL, Wright G, Xiao W, Powell J, Jiang JK, Thomas CJ, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM (2010) Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463(7277):88–92

    Article  PubMed  CAS  Google Scholar 

  • Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M, Letai A (2007) BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell 12(2):171–185

    Article  PubMed  CAS  Google Scholar 

  • Deutsch AJ, Fruhwirth M, Aigelsreiter A, Cerroni L, Neumeister P (2009) Primary cutaneous marginal zone B-cell lymphomas are targeted by aberrant somatic hypermutation. J Invest Dermatol 129(2):476–479

    Article  PubMed  CAS  Google Scholar 

  • Dunleavy K, Pittaluga S, Czuczman MS, Dave SS, Wright G, Grant N, Shovlin M, Jaffe ES, Janik JE, Staudt LM, Wilson WH (2009) Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood 113(24):6069–6076

    Article  PubMed  CAS  Google Scholar 

  • Ferch U, Kloo B, Gewies A, Pfander V, Duwel M, Peschel C, Krappmann D, Ruland J (2009) Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 206(11):2313–2320

    Article  PubMed  CAS  Google Scholar 

  • Feuerhake F, Kutok JL, Monti S, Chen W, LaCasce AS, Cattoretti G, Kurtin P, Pinkus GS, de Leval L, Harris NL, Savage KJ, Neuberg D, Habermann TM, Dalla-Favera R, Golub TR, Aster JC, Shipp MA (2005) NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes. Blood 106(4):1392–1399

    Article  PubMed  CAS  Google Scholar 

  • Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, Schaefer-Cutillo J, De Vos S, Sinha R, Leonard JP, Cripe LD, Gregory SA, Sterba MP, Lowe AM, Levy R, Shipp MA (2010) Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 115(13):2578–2585

    Article  PubMed  CAS  Google Scholar 

  • Fu K, Weisenburger DD, Choi WW, Perry KD, Smith LM, Shi X, Hans CP, Greiner TC, Bierman PJ, Bociek RG, Armitage JO, Chan WC, Vose JM (2008) 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 26(28):4587–4594

    Article  PubMed  CAS  Google Scholar 

  • Fugmann SD, Lee AI, Shockett PE, Villey IJ, Schatz DG (2000) The RAG proteins and V(D)J recombination: complexes, ends, and transposition. Annu Rev Immunol 18:495–527

    Article  PubMed  CAS  Google Scholar 

  • Gagyi E, Balogh Z, Bodor C, Timar B, Reiniger L, Deak L, Csomor J, Csernus B, Szepesi A, Matolcsy A (2008) Somatic hypermutation of IGVH genes and aberrant somatic hypermutation in follicular lymphoma without BCL-2 gene rearrangement and expression. Haematologica 93(12):1822–1828

    Article  PubMed  CAS  Google Scholar 

  • Gaidano G, Pasqualucci L, Capello D, Berra E, Deambrogi C, Rossi D, Maria Larocca L, Gloghini A, Carbone A, Dalla-Favera R (2003) Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma. Blood 102(5):1833–1841

    Article  PubMed  CAS  Google Scholar 

  • Goossens T, Klein U, Kuppers R (1998) Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease. Proc Natl Acad Sci U S A 95(5):2463–2468

    Article  PubMed  CAS  Google Scholar 

  • Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O’Donnell E, Chapuy B, Takeyama K, Neuberg D, Golub TR, Kutok JL, Shipp MA (2010) Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 116(17):3268–3277

    Article  PubMed  CAS  Google Scholar 

  • Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, Miller RA, Buggy JJ (2010) The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A 107(29):13075–13080

    Article  PubMed  CAS  Google Scholar 

  • Jost PJ, Ruland J (2007) Aberrant NF-kappaB signaling in lymphoma: mechanisms, consequences, and therapeutic implications. Blood 109(7):2700–2707

    PubMed  CAS  Google Scholar 

  • Klein U, Dalla-Favera R (2008) Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol 8(1):22–33

    Article  PubMed  CAS  Google Scholar 

  • Klein U, Goossens T, Fischer M, Kanzler H, Braeuninger A, Rajewsky K, Kuppers R (1998) Somatic hypermutation in normal and transformed human B cells. Immunol Rev 162:261–280

    Article  PubMed  CAS  Google Scholar 

  • Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, de Jong D, Maartense E, Schuuring E, Kluin PM (1998) Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. Blood 92(9):3152–3162

    PubMed  CAS  Google Scholar 

  • Kuppers R, Dalla-Favera R (2001) Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 20(40):5580–5594

    Article  PubMed  CAS  Google Scholar 

  • Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, Dave SS, Zhao H, Xu W, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Chan WC, Staudt LM (2008a) Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319(5870):1676–1679

    Article  PubMed  CAS  Google Scholar 

  • Lenz G, Nagel I, Siebert R, Roschke AV, Sanger W, Wright GW, Dave SS, Tan B, Zhao H, Rosenwald A, Muller-Hermelink HK, Gascoyne RD, Campo E, Jaffe ES, Smeland EB, Fisher RI, Kuehl WM, Chan WC, Staudt LM (2007) Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma. J Exp Med 204(3):633–643

    Article  PubMed  CAS  Google Scholar 

  • Lenz G, Staudt LM (2010) Aggressive lymphomas. N Engl J Med 362(15):1417–1429

    Article  PubMed  CAS  Google Scholar 

  • Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, Weisenburger DD, Greiner TC, Armitage JO, Kyle A, May L, Gascoyne RD, Connors JM, Troen G, Holte H, Kvaloy S, Dierickx D, Verhoef G, Delabie J, Smeland EB, Jares P, Martinez A, Lopez-Guillermo A, Montserrat E, Campo E, Braziel RM, Miller TP, Rimsza LM, Cook JR, Pohlman B, Sweetenham J, Tubbs RR, Fisher RI, Hartmann E, Rosenwald A, Ott G, Muller-Hermelink HK, Wrench D, Lister TA, Jaffe ES, Wilson WH, Chan WC, Staudt LM (2008b) Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 359(22):2313–2323

    Article  PubMed  CAS  Google Scholar 

  • Lenz G, Wright GW, Emre NC, Kohlhammer H, Dave SS, Davis RE, Carty S, Lam LT, Shaffer AL, Xiao W, Powell J, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Campo E, Jaffe ES, Delabie J, Smeland EB, Rimsza LM, Fisher RI, Weisenburger DD, Chan WC, Staudt LM (2008c) Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A 105(36):13520–13525

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Climent JA, Fontan L, Gascoyne RD, Siebert R, Prosper F (2010) Lymphoma stem cells: enough evidence to support their existence? Haematologica 95(2):293–302

    Article  PubMed  CAS  Google Scholar 

  • Monroe JG (2006) ITAM-mediated tonic signalling through pre-BCR and BCR complexes. Nat Rev Immunol 6(4):283–294

    Article  PubMed  CAS  Google Scholar 

  • 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 MA (2005) Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 105(5):1851–1861

    Article  PubMed  CAS  Google Scholar 

  • Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F, Yap D, Humphries RK, Griffith OL, Shah S, Zhu H, Kimbara M, Shashkin P, Charlot JF, Tcherpakov M, Corbett R, Tam A, Varhol R, Smailus D, Moksa M, Zhao Y, Delaney A, Qian H, Birol I, Schein J, Moore R, Holt R, Horsman DE, Connors JM, Jones S, Aparicio S, Hirst M, Gascoyne RD, Marra MA (2010) Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet 42(2):181–185

    Article  PubMed  CAS  Google Scholar 

  • Mottok A, Renne C, Seifert M, Oppermann E, Bechstein W, Hansmann ML, Kuppers R, Brauninger A (2009) Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities. Blood 114(20):4503–4506

    Article  PubMed  CAS  Google Scholar 

  • Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102(5):553–563

    Article  PubMed  CAS  Google Scholar 

  • Muschen M, Rajewsky K, Kronke M, Kuppers R (2002) The origin of CD95-gene mutations in B-cell lymphoma. Trends Immunol 23(2):75–80

    Article  PubMed  CAS  Google Scholar 

  • Ngo VN, Davis RE, Lamy L, Yu X, Zhao H, Lenz G, Lam LT, Dave S, Yang L, Powell J, Staudt LM (2006) A loss-of-function RNA interference screen for molecular targets in cancer. Nature 441(7089):106–110

    Article  PubMed  CAS  Google Scholar 

  • Nogai H, Dorken B, Lenz G (2011) Pathogenesis of non-Hodgkin’s lymphoma. J Clin Oncol 29(14):1803–1811

    Article  PubMed  CAS  Google Scholar 

  • Papavasiliou FN, Schatz DG (2000) Cell-cycle-regulated DNA double-stranded breaks in somatic hypermutation of immunoglobulin genes. Nature 408(6809):216–221

    Article  PubMed  CAS  Google Scholar 

  • Pasqualucci L, Bhagat G, Jankovic M, Compagno M, Smith P, Muramatsu M, Honjo T, Morse HC, Nussenzweig MC, Dalla-Favera R (2008) AID is required for germinal center-derived lymphomagenesis. Nat Genet 40(1):108–112

    Article  PubMed  CAS  Google Scholar 

  • Pasqualucci L, Compagno M, Houldsworth J, Monti S, Grunn A, Nandula SV, Aster JC, Murty VV, Shipp MA, Dalla-Favera R (2006) Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med 203(2):311–317

    Article  PubMed  CAS  Google Scholar 

  • Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, Rossi D, Chadburn A, Murty VV, Mullighan CG, Gaidano G, Rabadan R, Brindle PK, Dalla-Favera R (2011) Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 471(7337):189–195

    Article  PubMed  CAS  Google Scholar 

  • Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kuppers R, Dalla-Favera R (2001) Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 412(6844):341–346

    Article  PubMed  CAS  Google Scholar 

  • Polo JM, Dell’Oso T, Ranuncolo SM, Cerchietti L, Beck D, Da Silva GF, Prive GG, Licht JD, Melnick A (2004) Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells. Nat Med 10(12):1329–1335

    Article  PubMed  CAS  Google Scholar 

  • Polo JM, Juszczynski P, Monti S, Cerchietti L, Ye K, Greally JM, Shipp M, Melnick A (2007) Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas. Proc Natl Acad Sci U S A 104(9):3207–3212

    Article  PubMed  CAS  Google Scholar 

  • Rajewsky K (1996) Clonal selection and learning in the antibody system. Nature 381(6585):751–758

    Article  PubMed  CAS  Google Scholar 

  • Ramiro AR, Jankovic M, Eisenreich T, Difilippantonio S, Chen-Kiang S, Muramatsu M, Honjo T, Nussenzweig A, Nussenzweig MC (2004) AID is required for c-myc/IgH chromosome translocations in vivo. Cell 118(4):431–438

    Article  PubMed  CAS  Google Scholar 

  • Robertson MJ, Kahl BS, Vose JM, de Vos S, Laughlin M, Flynn PJ, Rowland K, Cruz JC, Goldberg SL, Musib L, Darstein C, Enas N, Kutok JL, Aster JC, Neuberg D, Savage KJ, LaCasce A, Thornton D, Slapak CA, Shipp MA (2007) 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 25(13):1741–1746

    Article  PubMed  CAS  Google Scholar 

  • Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, Gascoyne RD, Muller-Hermelink HK, Smeland EB, Giltnane JM, Hurt EM, Zhao H, Averett L, Yang L, Wilson WH, Jaffe ES, Simon R, Klausner RD, Powell J, Duffey PL, Longo DL, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Montserrat E, Lopez-Guillermo A, Grogan TM, Miller TP, LeBlanc M, Ott G, Kvaloy S, Delabie J, Holte H, Krajci P, Stokke T, Staudt LM (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346(25):1937–1947

    Article  PubMed  Google Scholar 

  • Ruefli-Brasse AA, French DM, Dixit VM (2003) Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase. Science 302(5650):1581–1584

    Article  PubMed  CAS  Google Scholar 

  • Schatz DG, Ji Y (2011) Recombination centres and the orchestration of V(D)J recombination. Nat Rev Immunol 11(4):251–263

    Article  PubMed  CAS  Google Scholar 

  • Schmidlin H, Diehl SA, Nagasawa M, Scheeren FA, Schotte R, Uittenbogaart CH, Spits H, Blom B (2008) Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression. Blood 112(5):1804–1812

    Article  PubMed  CAS  Google Scholar 

  • Shipp MA (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 329(14):987–994

    Article  Google Scholar 

  • Shipp MA, Ross KN, Tamayo P, Weng AP, Kutok JL, Aguiar RC, Gaasenbeek M, Angelo M, Reich M, Pinkus GS, Ray TS, Koval MA, Last KW, Norton A, Lister TA, Mesirov J, Neuberg DS, Lander ES, Aster JC, Golub TR (2002) Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 8(1):68–74

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow SH, International Agency for Research on Cancer, World Health Organization (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. World health organization classification of tumours, 4th edn. International Agency for Research on Cancer, Lyon, France

    Google Scholar 

  • Takahashi H, Feuerhake F, Kutok JL, Monti S, Dal Cin P, Neuberg D, Aster JC, Shipp MA (2006) FAS death domain deletions and cellular FADD-like interleukin 1beta converting enzyme inhibitory protein (long) overexpression: alternative mechanisms for deregulating the extrinsic apoptotic pathway in diffuse large B-cell lymphoma subtypes. Clin Cancer Res 12(11 Pt 1):3265–3271

    Article  PubMed  CAS  Google Scholar 

  • Tam W, Gomez M, Chadburn A, Lee JW, Chan WC, Knowles DM (2006) Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas. Blood 107(10):4090–4100

    Article  PubMed  CAS  Google Scholar 

  • Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM (2003) A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci U S A 100(17):9991–9996

    Article  PubMed  CAS  Google Scholar 

  • Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, Morin RD, Mungall AJ, Meissner B, Boyle M, Marquez VE, Marra MA, Gascoyne RD, Humphries RK, Arrowsmith CH, Morin GB, Aparicio SA (2011) Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood 117(8):2451–2459

    Article  PubMed  CAS  Google Scholar 

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  1. Institute of Hematology and Transfusion Medicine, Indiry Gandhi 14, 02-776, Warsaw, Poland

    Przemysław Juszczyński & Krzysztof Warzocha

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  1. Przemysław Juszczyński
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  2. Krzysztof Warzocha
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Correspondence to Przemysław Juszczyński .

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  1. International Institute of Molecular and, Trojdena 4, Warszawa, 02-109, Poland

    Michal Witt

  2. , Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszynska 32, Poznan, 60479, Poland

    Malgorzata Dawidowska

  3. , Department of Pediatric Hematology, Silesian Academy of Medicine, 3 Maja 13-15, Zabrze, 41800, Poland

    Tomasz Szczepanski

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Juszczyński, P., Warzocha, K. (2012). Molecular Pathogenesis of Aggressive B-cell Lymphomas. In: Witt, M., Dawidowska, M., Szczepanski, T. (eds) Molecular Aspects of Hematologic Malignancies. Principles and Practice. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29467-9_3

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