Abstract
Lymphomas of mucosa-associated lymphoid tissue (MALT) are typically present at sites such as the stomach, lung or urinary tract, where lymphoid tissues scatter in mucosa lamina propria, intra- or sub-epithelial cells. The infection of certain pathogens, such as Helicobacter pylori, Chlamydophila psittaci, Borrelia burgdorferi, hepatitis C virus, or certain autoantigens cause these sites to generate a germinal center called the “acquired lymphoid tissue”. The molecular pathogenesis of MALT lymphoma is a multi-step process. Receptor signaling, such as the contact stimulation of B cell receptors and CD4 positive T cells mediated by CD40/CD40-ligand and T helper cell type 2 cytokines like interleukin-4, contributes to tumor cell proliferation. A number of genetic alterations have been identified in MALT lymphoma, and among them are important translocations, such as t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32). Fusion proteins generated by these translocations share the same NF-κB signaling pathway, which is activated by the caspase activation and recruitment domain containing molecules of the membrane associated guanylate kinase family, B cell lymphoma-10 and MALT1 (CBM) protein complex. They act downstream of cell surface receptors, such as B cell receptors, T cell receptors, B cell activating factors and Toll-like receptors, and participate in the biological process of MALT lymphoma. The discovery of therapeutic drugs that exclusively inhibit the antigen receptor signaling pathway will be beneficial for the treatment of B cell lymphomas in the future.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Isaacson PG. Mucosa-associated lymphoid tissue lymphoma. Semin Hematol, 1999, 36: 139–147
Sackmann M, Morgner A, Rudolph B, Neubauer A, Thiede C, Schulz H, Kraemer W, Boersch G, Rohde P, Seifert E, Stolte M, Bayerdoerffer E. Regression of gastric MALT lymphoma after eradication of Helicobacter pylori is predicted by endosonographic staging. MALT Lymphoma Study Group. Gastroenterology, 1997, 113: 1087–1090
Liu H, Ruskon-Fourmestraux A, Lavergne-Slove A, Ye H, Molina T, Bouhnik Y, Hamoudi RA, Diss TC, Dogan A, Megraud F, Rambaud JC, Du MQ, Isaacson PG. Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. Lancet, 2001, 357: 39–40
Lucas PC, McAllister-Lucas LM, Nunez G. NF-kappaB signaling in lymphocytes: a new cast of characters. J Cell Sci, 2004, 117: 31–39
Hussell T, Isaacson PG, Crabtree JE, Spencer J. The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet, 1993, 342: 571–574
Mueller A, O’Rourke J, Grimm J, Guillemin K, Dixon MF, Lee A, Falkow S. Distinct gene expression profiles characterize the histopathological stages of disease in Helicobacter-induced mucosa-associated lymphoid tissue lymphoma. Proc Natl Acad Sci USA, 2003, 100: 1292–1297
Lee A, O’Rourke J, Enno A. Gastric mucosa-associated lymphoid tissue lymphoma: implications of animal models on pathogenic and therapeutic considerations—mouse models of gastric lymphoma. Recent Results Cancer Res, 2000, 156: 42–51
Ye H, Liu H, Attygalle A, Wotherspoon AC, Nicholson AG, Charlotte F, Leblond V, Speight P, Goodlad J, Lavergne-Slove A, Martin-Subero JI, Siebert R, Dogan A, Isaacson PG, Du MQ. Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H. pylori in gastric MALT lymphoma. Blood, 2003, 102: 1012–1018
Israel DA, Peek RM. Pathogenesis of Helicobacter pylori-induced gastric inflammation. Aliment Pharmacol Ther, 2001, 15: 1271–1290
Zambon CF, Navaglia F, Basso D, Rugge M, Plebani M. Helicobacter pylori babA2, cagA, and s1 vacA genes work synergistically in causing intestinal metaplasia. J Clin Pathol, 2003, 56: 287–291
Collina F, De Chiara A, De Renzo A, De Rosa G, Botti G, Franco R. Chlamydia psittaci in ocular adnexa MALT lymphoma: a possible role in lymphomagenesis and a different geographical distribution. Infect Agents Cancer, 2012, 7: 8
Dagklis A, Ponzoni M, Govi S, Cangi MG, Pasini E, Charlotte F, Vino A, Doglioni C, Davi F, Lossos IS, Ntountas I, Papadaki T, Dolcetti R, Ferreri AJ, Stamatopoulos K, Ghia P. Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation. Leukemia, 2012, 26: 814–821
Garbe C, Stein H, Dienemann D, Orfanos CE. Borrelia burgdorferiassociated cutaneous B cell lymphoma: clinical and immunohistologic characterization of four cases. J Am Acad Dermatol, 1991, 24: 584–590
Goodlad JR, Davidson MM, Hollowood K, Batstone P, Ho-Yen DO. Borrelia burgdorferi-associated cutaneous marginal zone lymphoma: a clinicopathological study of two cases illustrating the temporal progression of B. burgdorferi-associated B-cell proliferation in the skin. Histopathology, 2000, 37: 501–508
Monari P, Farisoglio C, Calzavara Pinton PG. Borrelia burgdorferiassociated primary cutaneous marginal-zone B-cell lymphoma: a case report. Dermatology, 2007, 215: 229–232
Kalume F, Lee SM, Morcos Y, Callaway JC, Levin MC. Molecular mimicry: cross-reactive antibodies from patients with immunemediated neurologic disease inhibit neuronal firing. J Neurosci Res, 2004, 77: 82–89
Luppi M, Longo G, Ferrari MG, Ferrara L, Marasca R, Barozzi P, Morselli M, Emilia G, Torelli G. Additional neoplasms and HCV infection in low-grade lymphoma of MALT type. Br J Haematol, 1996, 94: 373–375
Arcaini L, Burcheri S, Rossi A, Paulli M, Bruno R, Passamonti F, Brusamolino E, Molteni A, Pulsoni A, Cox MC, Orsucci L, Fabbri A, Frezzato M, Voso MT, Zaja F, Montanari F, Merli M, Pascutto C, Morra E, Cortelazzo S, Lazzarino M. Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT. Ann Oncol, 2007, 18: 346–350
Peveling-Oberhag J, Arcaini L, Hansmann ML, Zeuzem S. Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management. J Hepatol, 2013, 59: 169–177
Royer B, Cazals-Hatem D, Sibilia J, Agbalika F, Cayuela JM, Soussi T, Maloisel F, Clauvel JP, Brouet JC, Mariette X. Lymphomas in patients with Sjogren’s syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses. Blood, 1997, 90: 766–775
Zhao WC, Dai JJ. Primary malignant lymphoma of thyroid gland:clinical analysis of 28 cases. Chin J Cancer, 2003, 22: 1224–1227
Tierens A, Delabie J, Pittaluga S, Driessen A, DeWolf-Peeters C. Mutation analysis of the rearranged immunoglobulin heavy chain genes of marginal zone cell lymphomas indicates an origin from different marginal zone B lymphocyte subsets. Blood, 1998, 91: 2381–2386
Du M, Diss TC, Xu C, Peng H, Isaacson PG, Pan L. Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion. Leukemia, 1996, 10: 1190–1197
Fujimori K, Shimodaira S, Akamatsu T, Furihata K, Katsuyama T, Hosaka S. Effect of Helicobacter pylori eradication on ongoing mutation of immunoglobulin genes in gastric MALT lymphoma. Br J Cancer, 2005, 92: 312–319
Hussell T, Isaacson PG, Crabtree JE, Spencer J. Helicobacter pylori-specific tumour-infiltrating T cells provide contact dependent help for the growth of malignant B cells in low-grade gastric lymphoma of mucosa-associated lymphoid tissue. J Pathol, 1996, 178: 122–127
Craig VJ, Cogliatti SB, Arnold I, Gerke C, Balandat JE, Wundisch T, Muller A. B-cell receptor signaling and CD40 ligand-independent T cell help cooperate in Helicobacter-induced MALT lymphomagenesis. Leukemia, 2010, 24: 1186–1196
Voo KS, Foglietta M, Percivalle E, Chu F, Nattamai D, Harline M, Lee ST, Bover L, Lin HY, Baladandayuthapani V, Delgado D, Luong A, Davis RE, Kwak LW, Liu YJ, Neelapu SS. Selective targeting of Toll-like receptors and OX40 inhibit regulatory T-cell function in follicular lymphoma. Int J Cancer, 2014, 135: 2834–2846
Pinheiro D, Chang YM, Bryant H, Szladovits B, Dalessandri T, Davison LJ, Yallop E, Mills E, Leo C, Lara A, Stell A, Polton G, Garden OA. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. PLoS One, 2014, 9: e105027
Garcia M, Bellosillo B, Sanchez-Gonzalez B, Garcia-Payarols F, Seoane A, Ferrer AM, Gimeno E, Barranco LE, Torner A, Sole F, Besses C, Serrano S, Salar A. Study of regulatory T-cells in patients with gastric malt lymphoma: influence on treatment response and outcome. PLoS One, 2012, 7: e51681
Adam P, Schmausser B, Gobeler-Kolve M, Muller-Hermelink HK, Eck M. Gastric extranodal marginal zone B-cell lymphomas of MALT type exclusively express Toll-like receptor 4 in contrast to other lymphomas infiltrating the stomach. Ann Oncol, 2008, 19: 566–569
Gruss HJ, Dower SK. Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. Blood, 1995, 85: 3378–3404
Nagata S. Apoptosis and autoimmune diseases. IUBMB Life, 2006, 58: 358–362
Huard B, McKee T, Bosshard C, Durual S, Matthes T, Myit S, Donze O, Frossard C, Chizzolini C, Favre C, Zubler R, Guyot JP, Schneider P, Roosnek E. APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa. J Clin Invest, 2008, 118: 2887–2895
Nakajima N, Kuwayama H, Ito Y, Iwasaki A, Arakawa Y. Helicobacter pylori, neutrophils, interleukins, and gastric epithelial proliferation. J Clin Gastroenterol, 1997, 25 Suppl 1: S198–S202
Bagaitkar J, Pech NK, Ivanov S, Austin A, Zeng MY, Pallat S, Huang G, Randolph GJ, Dinauer MC. NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating IL-1alpha/G-CSF axis. Blood, 2015, doi: http://dx.doi.org/10.1182/ blood-2015-05-644773
Zha L, Chen J, Sun S, Mao L, Chu X, Deng H, Cai J, Li X, Liu Z, Cao W. Soyasaponins can blunt inflammation by inhibiting the reactive oxygen species-mediated activation of PI3K/Akt/NF-kB pathway. PLoS One, 2014, 9: e107655
Gang C, Qiang C, Xiangli C, Shifen P, Chong S, Lihong L. Puerarin suppresses angiotensin II-induced cardiac hypertrophy by inhibiting NADPH oxidase activation and oxidative stress-triggered AP-1 signaling pathways. J Pharm Pharm Sci, 2015, 18: 235–248
Chua YL, Dufour E, Dassa EP, Rustin P, Jacobs HT, Taylor CT, Hagen T. Stabilization of hypoxia-inducible factor-1alpha protein in hypoxia occurs independently of mitochondrial reactive oxygen species production. J Biol Chem, 2010, 285: 31277–31284
Yoon S, Woo SU, Kang JH, Kim K, Kwon MH, Park S, Shin HJ, Gwak HS, Chwae YJ. STAT3 transcriptional factor activated by reactive oxygen species induces IL6 in starvation-induced autophagy of cancer cells. Autophagy, 2010, 6: 1125–1138
Kim SJ, Jung HJ, Lim CJ. Reactive oxygen species-dependent down-regulation of tumor suppressor genes PTEN, USP28, DRAM, TIGAR, and CYLD under oxidative stress. Biochem Genet, 2013, 51: 901–915
Bessede E, Copie-Bergman C, Lehours P, Levy M, Leroy K, Baia M, Riou A, Megraud F, Delchier JC, Salles N. Is elevated gastric tissue NOX2 associated with lymphoma of mucosa-associated lymphoid tissue? Antioxid Redox Signal, 2012, 16: 1205–1211
Burger JA, Gribben JG. The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: insight into disease biology and new targeted therapies. Semin Cancer Biol, 2014, 24: 71–81
Munari F, Lonardi S, Cassatella MA, Doglioni C, Cangi MG, Amedei A, Facchetti F, Eishi Y, Rugge M, Fassan M, De Bernard M, D'Elios MM, Vermi W. Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma. Blood, 2011, 117: 6612–6616
Barone F, Bombardieri M, Rosado MM, Morgan PR, Challacombe SJ, De Vita S, Carsetti R, Spencer J, Valesini G, Pitzalis C. CXCL13, CCL21, and CXCL12 expression in salivary glands of patients with Sjogren’s syndrome and MALT lymphoma: association with reactive and malignant areas of lymphoid organization. J Immunol, 2008, 180: 5130–5140
Ferreira-Chagas B, Lasne G, Dupouy S, Gallois A, Morgner A, Menard A, Megraud F, Lehours P. In vitro proinflammatory properties of Helicobacter pylori strains causing low-grade gastric MALT lymphoma. Helicobacter, 2007, 12: 616–617
Peng H, Diss T, Isaacson PG, Pan L. c-myc gene abnormalities in mucosa-associated lymphoid tissue (MALT) lymphomas. J Pathol, 1997, 181: 381–386
Du M, Peng H, Singh N, Isaacson PG, Pan L. The accumulation of p53 abnormalities is associated with progression of mucosaassociated lymphoid tissue lymphoma. Blood, 1995, 86: 4587–4593
Seeberger H, Knorr C, Muller-Hermelink HK, Greiner A. Impaired CD95-(Fas,APO-1-)apoptosis regulation is a progression factor in early MALT-type lymphoma genesis. Med Klin (Munich), 2001, 96: 9–14
Kondo T, Oka T, Sato H, Shinnou Y, Washio K, Takano M, Morito T, Takata K, Ohara N, Ouchida M, Shimizu K, Yoshino T. Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma. Int J Oncol, 2009, 35: 547–557
Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J, 1997, 16: 6914–6925
Uren AG, O’Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM. Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell, 2000, 6: 961–967
Alpen B, Neubauer A, Dierlamm J, Marynen P, Thiede C, Bayerdorfer E, Stolte M. Translocation t(11;18) absent in early gastric marginal zone B-cell lymphoma of MALT type responding to eradication of Helicobacter pylori infection. Blood, 2000, 95: 4014–4015
Zhou H, Du MQ, Dixit VM. Constitutive NF-kappaB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity. Cancer Cell, 2005, 7: 425–431
Toracchio S, Ota H, De Jong D, Wotherspoon A, Rugge M, Graham DY, Samani A, El-Zimaity HM. Translocation t(11;18)(q21;q21) in gastric B-cell lymphomas. Cancer Sci, 2009, 100: 881–887
Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ. Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell, 1999, 96: 35–45
Ye H, Dogan A, Karran L, Willis TG, Chen L, Wlodarska I, Dyer MJ, Isaacson PG, Du MQ. BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma. Am J Pathol, 2000, 157: 1147–1154
Ruland J, Duncan GS, Elia A, del Barco Barrantes I, Nguyen L, Plyte S, Millar DG, Bouchard D, Wakeham A, Ohashi PS, Mak TW. Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Cell, 2001, 104: 33–42
Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott G, Raderer M, Chott A. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood, 2003, 101: 2335–2339
Sagaert X, Laurent M, Baens M, Wlodarska I, De Wolf-Peeters C. MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells. Mod Pathol, 2006, 19: 225–232
Streubel B, Simonitsch-Klupp I, Mullauer L, Lamprecht A, Huber D, Siebert R, Stolte M, Trautinger F, Lukas J, Puspok A, Formanek M, Assanasen T, Muller-Hermelink HK, Cerroni L, Raderer M, Chott A. Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites. Leukemia, 2004, 18: 1722–1726
Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G. Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem, 2001, 276: 19012–19019
Banham AH, Beasley N, Campo E, Fernandez PL, Fidler C, Gatter K, Jones M, Mason DY, Prime JE, Trougouboff P, Wood K, Cordell JL. The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. Cancer Res, 2001, 61: 8820–8829
Katoh M, Katoh M. Human FOX gene family (Review). Int J Oncol, 2004, 25: 1495–1500
Sagaert X, De Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, Wlodarska I, De Wolf-Peeters C. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol, 2006, 24: 2490–2497
Wu L, Lu P, Ma W, Chu C, Xu H, Qi H. Identification of a new isoform of the murine Sh2d1a gene and its functional implications. Sci China Life Sci, 2014, 57: 81–87
Marsh RA, Madden L, Kitchen BJ, Mody R, McClimon B, Jordan MB, Bleesing JJ, Zhang K, Filipovich AH. XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease. Blood, 2010, 116: 1079–1082
Ansell SM, Akasaka T, McPhail E, Manske M, Braggio E, Price-Troska T, Ziesmer S, Secreto F, Fonseca R, Gupta M, Law M, Witzig TE, Dyer MJ, Dogan A, Cerhan JR, Novak AJ. t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth. Blood, 2012, 120: 3949–3957
Musilova K, Mraz M. MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia, 2015, 29: 1004–1017
Ma X, Becker Buscaglia LE, Barker JR, Li Y. MicroRNAs in NF-kappaB signaling. J Mol Cell Biol, 2011, 3: 159–166
Huang X, Shen Y, Liu M, Bi C, Jiang C, Iqbal J, McKeithan TW, Chan WC, Ding SJ, Fu K. Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma. Am J Pathol, 2012, 181: 26–33
Rai D, Kim SW, McKeller MR, Dahia PL, Aguiar RC. Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and lymphomagenesis. Proc Natl Acad Sci USA, 2010, 107: 3111–3116
Mraz M, Kipps TJ. MicroRNAs and B cell receptor signaling in chronic lymphocytic leukemia. Leukemia Lymphoma, 2013, 54: 1836–1839
Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA, 2005, 102: 13944–13949
Park SY, Lee JH, Ha M, Nam JW, Kim VN. miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol, 2009, 16: 23–29
Craig VJ, Cogliatti SB, Imig J, Renner C, Neuenschwander S, Rehrauer H, Schlapbach R, Dirnhofer S, Tzankov A, Muller A. Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood, 2011, 117: 6227–6236
Sandhu SK, Volinia S, Costinean S, Galasso M, Neinast R, Santhanam R, Parthun MR, Perrotti D, Marcucci G, Garzon R, Croce CM. miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Emu-miR-155 transgenic mouse model. Proc Natl Acad Sci USA, 2012, 109: 20047–20052
Du MQ. MALT lymphoma: many roads lead to nuclear factor-kappab activation. Histopathology, 2011, 58: 26–38
Shinohara H, Maeda S, Watarai H, Kurosaki T. IkappaB kinase beta-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10 MALT1 complex formation in B cells. J Exp Med, 2007, 204: 3285–3293
Basak S, Shih VF, Hoffmann A. Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system. Mol Cell Biol, 2008, 28: 3139–3150
Scudiero I, Zotti T, Ferravante A, Vessichelli M, Vito P, Stilo R. Alternative splicing of CARMA2/CARD14 transcripts generates protein variants with differential effect on NF-kappaB activation and endoplasmic reticulum stress-induced cell death. J Cell Physiol, 2011, 226: 3121–3131
Stilo R, Varricchio E, Liguoro D, Leonardi A, Vito P. A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-kappaB. J Cell Sci, 2008, 121: 1165–1171
Grabiner BC, Blonska M, Lin PC, You Y, Wang D, Sun J, Darnay BG, Dong C, Lin X. CARMA3 deficiency abrogates G proteincoupled receptor-induced NF-kappaB activation. Genes Dev, 2007, 21: 984–996
Wang D, Matsumoto R, You Y, Che T, Lin XY, Gaffen SL, Lin X. CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological synapse through CARMA1. Mol Cell Biol, 2004, 24: 164–171
Lee KY, D’Acquisto F, Hayden MS, Shim JH, Ghosh S. PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation. Science, 2005, 308: 114–118
Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno- Garcia ME, Ovechkina YL, Rawlings DJ. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Immunity, 2005, 23: 561–574
Inoue J, Ishida T, Tsukamoto N, Kobayashi N, Naito A, Azuma S, Yamamoto T. Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling. Exp Cell Res, 2000, 254: 14–24
Sun L, Deng L, Ea CK, Xia ZP, Chen ZJ. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell, 2004, 14: 289–301
Newton K, Dixit VM. Mice lacking the CARD of CARMA1 exhibit defective B lymphocyte development and impaired proliferation of their B and T lymphocytes. Curr Biol, 2003, 13: 1247–1251
Lucas PC, Kuffa P, Gu S, Kohrt D, Kim DS, Siu K, Jin X, Swenson J, McAllister-Lucas LM. A dual role for the API2 moiety in API2- MALT1-dependent NF-kappaB activation: heterotypic oligomerization and TRAF2 recruitment. Oncogene, 2007, 26: 5643–5654
Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell, 1995, 83: 1243–1252
Rosebeck S, Madden L, Jin X, Gu S, Apel IJ, Appert A, Hamoudi RA, Noels H, Sagaert X, van Loo P, Baens M, Du MQ, Lucas PC, McAllister-Lucas LM. Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-kappaB activation. Science, 2011, 331: 468–472
Rosebeck S, Rehman AO, Apel IJ, Kohrt D, Appert A, O’Donnell MA, Ting AT, Du MQ, Baens M, Lucas PC, McAllister-Lucas LM. The API2-MALT1 fusion exploits TNFR pathway-associated RIP1 ubiquitination to promote oncogenic NF-kappaB signaling. Oncogene, 2014, 33: 2520–2530
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. 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: 1741–1746
Ferch U, Kloo B, Gewies A, Pfander V, Duwel M, Peschel C, Krappmann D, Ruland J. Inhibition of MALT1 protease activity is selectively toxic for activated B cell-like diffuse large B cell lymphoma cells. J Exp Med, 2009, 206: 2313–2320
McAllister-Lucas LM, Baens M, Lucas PC. MALT1 protease: a new therapeutic target in B lymphoma and beyond? Clin Cancer Res, 2011, 17: 6623–6631
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at link.springer.com
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Zhang, Y., Wei, Z., Li, J. et al. Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue—from (auto)antigen driven selection to the activation of NF-κB signaling. Sci. China Life Sci. 58, 1246–1255 (2015). https://doi.org/10.1007/s11427-015-4977-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-015-4977-2