1932

Abstract

Peripheral T cell lymphomas (PTCLs) are highly heterogeneous tumors, displaying distinct clinical and biological features. The pathogenesis and normal counterpart of such entities have been elusive for decades. Recent studies have, however, disclosed key mechanisms of peripheral T cell transformation, including () the deregulation of signaling pathways controlling T cell development, differentiation, and maturation; () the remodeling of the peritumor microenvironment; and () the virus-mediated rewiring of T cell biology. Uncovering the molecular mechanisms of T cell transformation will help elucidate the peculiar clinical and pathological features of each PTCL entity and will lead to the characterization of novel antitumor therapies. These therapies will combine conventional and new-generation compounds with immune-modulating agents to ablate both the neoplastic cells and the tumor-supporting microenvironment. This review addresses the pathogenic mechanisms of PTCLs, with special attention paid to novel therapeutic strategies for the clinical management of such aggressive tumors.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-020117-043821
2018-01-24
2024-04-17
Loading full text...

Full text loading...

/deliver/fulltext/pathol/13/1/annurev-pathol-020117-043821.html?itemId=/content/journals/10.1146/annurev-pathol-020117-043821&mimeType=html&fmt=ahah

Literature Cited

  1. Swerdlow SH, Campo E, Harris NL, Jaffe EF, Pileri SA. 1.  et al. 2017. World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues Lyon, Fr.: Int. Agency Res. Cancer. Rev. 4th ed.
  2. Inghirami G, Pileri SA. 2.  2011. Anaplastic large-cell lymphoma. Semin. Diagn. Pathol. 28:190–201 [Google Scholar]
  3. Perry AM, Warnke RA, Hu Q, Gaulard P, Copie-Bergman C. 3.  et al. 2013. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood 122:3599–606 [Google Scholar]
  4. Pizzi M, Inghirami G. 4.  2017. Patient-derived tumor xenografts of lymphoproliferative disorders: Are they surrogates for the human disease?. Curr. Opin. Hematol. 24:384–92 [Google Scholar]
  5. Dow LE, Fisher J, O'Rourke KP, Muley A, Kastenhuber ER. 5.  et al. 2015. Inducible in vivo genome editing with CRISPR-Cas9. Nat. Biotechnol. 33:390–94 [Google Scholar]
  6. Inghirami G, Chan WC, Pileri S. 6. , AIRC 5xMille Consort. 2015. Peripheral T-cell and NK cell lymphoproliferative disorders: cell of origin, clinical and pathological implications. Immunol. Rev. 263:124–59 [Google Scholar]
  7. Josefowicz SZ. 7.  2013. Regulators of chromatin state and transcription in CD4 T-cell polarization. Immunology 139:299–308 [Google Scholar]
  8. Iqbal J, Weisenburger DD, Greiner TC, Vose JM, McKeithan T. 8.  et al. 2010. Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. Blood 115:1026–36 [Google Scholar]
  9. Piccaluga PP, Agostinelli C, Califano A, Carbone A, Fantoni L. 9.  et al. 2007. Gene expression analysis of angioimmunoblastic lymphoma indicates derivation from T follicular helper cells and vascular endothelial growth factor deregulation. Cancer Res 67:10703–10 [Google Scholar]
  10. Iqbal J, Wright G, Wang C, Rosenwald A, Gascoyne RD. 10.  et al. 2014. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood 123:2915–23 [Google Scholar]
  11. Huang Y, de Reynies A, de Leval L, Ghazi B, Martin-Garcia N. 11.  et al. 2009. Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood 115:1226–37 [Google Scholar]
  12. Sakata-Yanagimoto M. 12.  2015. Multistep tumorigenesis in peripheral T cell lymphoma. Int. J. Hematol. 102:523–27 [Google Scholar]
  13. Wilcox RA. 13.  2016. A three-signal model of T-cell lymphoma pathogenesis. Am. J. Hematol. 91:113–22 [Google Scholar]
  14. Smith-Garvin JE, Koretzky GA, Jordan MS. 14.  2009. T cell activation. Annu. Rev. Immunol. 27:591–619 [Google Scholar]
  15. Malissen B, Gregoire C, Malissen M, Roncagalli R. 15.  2014. Integrative biology of T cell activation. Nat. Immunol. 15:790–97 [Google Scholar]
  16. Chen L, Flies DB. 16.  2013. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol. 13:227–42 [Google Scholar]
  17. Croft M. 17.  2009. The role of TNF superfamily members in T-cell function and diseases. Nat. Rev. Immunol. 9:271–85 [Google Scholar]
  18. Ysebaert L, Michallet AS. 18.  2014. Bruton's tyrosine kinase inhibitors: lessons learned from bench-to-bedside (first) studies. Curr. Opin. Oncol. 26:463–68 [Google Scholar]
  19. Weissman IL, McGrath MS. 19.  1982. Retrovirus lymphomagenesis: relationship of normal immune receptors to malignant cell proliferation. Curr. Top. Microbiol. Immunol. 98:103–12 [Google Scholar]
  20. Jackow CM, Cather JC, Hearne V, Asano AT, Musser JM, Duvic M. 20.  1997. Association of erythrodermic cutaneous T-cell lymphoma, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor V beta gene expansion. Blood 89:32–40 [Google Scholar]
  21. Hu H, Johani K, Almatroudi A, Vickery K, Van Natta B. 21.  et al. 2016. Bacterial biofilm infection detected in breast implant-associated anaplastic large-cell lymphoma. Plast. Reconstr. Surg. 137:1659–69 [Google Scholar]
  22. dos Santos NR, Rickman DS, de Reynies A, Cormier F, Williame M. 22.  et al. 2007. Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia. Blood 109:3972–81 [Google Scholar]
  23. Kelly JA, Spolski R, Kovanen PE, Suzuki T, Bollenbacher J. 23.  et al. 2003. Stat5 synergizes with T cell receptor/antigen stimulation in the development of lymphoblastic lymphoma. J. Exp. Med. 198:79–89 [Google Scholar]
  24. Iqbal J, Wilcox R, Naushad H, Rohr J, Heavican TB. 24.  et al. 2016. Genomic signatures in T-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?. Blood Rev 30:89–100 [Google Scholar]
  25. Vallois D, Dobay MP, Morin RD, Lemonnier F, Missiaglia E. 25.  et al. 2016. Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. Blood 128:1490–502 [Google Scholar]
  26. Rohr J, Guo S, Huo J, Bouska A, Lachel C. 26.  et al. 2016. Recurrent activating mutations of CD28 in peripheral T-cell lymphomas. Leukemia 30:1062–70 [Google Scholar]
  27. Yoo HY, Kim P, Kim WS, Lee SH, Kim S. 27.  et al. 2016. Author reply to Comment on: Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma, by Yoo et al. Haematologica 101:e271 [Google Scholar]
  28. Vaque JP, Gomez-Lopez G, Monsalvez V, Varela I, Martinez N. 28.  et al. 2014. PLCG1 mutations in cutaneous T-cell lymphomas. Blood 123:2034–43 [Google Scholar]
  29. Sabattini E, Pizzi M, Tabanelli V, Baldin P, Sacchetti CS. 29.  et al. 2013. CD30 expression in peripheral T-cell lymphomas. Haematologica 98:e81–82 [Google Scholar]
  30. Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM. 30.  et al. 2010. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N. Engl. J. Med. 363:1812–21 [Google Scholar]
  31. Fanale MA, Younes A. 31.  2007. Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma. Drugs 67:333–50 [Google Scholar]
  32. Deng C, Pan B, O'Connor OA. 32.  2013. Brentuximab vedotin. Clin. Cancer Res. 19:22–27 [Google Scholar]
  33. Ambrogio C, Martinengo C, Voena C, Tondat F, Riera L. 33.  et al. 2009. NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells. Cancer Res 69:8611–19 [Google Scholar]
  34. Feldman AL, Dogan A, Smith DI, Law ME, Ansell SM. 34.  et al. 2011. Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. Blood 117:915–19 [Google Scholar]
  35. Pechloff K, Holch J, Ferch U, Schweneker M, Brunner K. 35.  et al. 2010. The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma. J. Exp. Med. 207:1031–44 [Google Scholar]
  36. Attygalle AD, Feldman AL, Dogan A. 36.  2013. ITK/SYK translocation in angioimmunoblastic T-cell lymphoma. Am. J. Surg. Pathol. 37:1456–57 [Google Scholar]
  37. Ntziachristos P, Tsirigos A, Van Vlierberghe P, Nedjic J, Trimarchi T. 37.  et al. 2012. Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nat. Med. 18:298–301 [Google Scholar]
  38. Palomero T, Lim WK, Odom DT, Sulis ML, Real PJ. 38.  et al. 2006. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. PNAS 103:18261–66 [Google Scholar]
  39. Sundaram M, Greenwald I. 39.  1993. Suppressors of a lin-12 hypomorph define genes that interact with both lin-12 and glp-1 in Caenorhabditis elegans. . Genetics 135:765–83 [Google Scholar]
  40. Tosello V, Ferrando AA. 40.  2013. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy. Ther. Adv. Hematol. 4:199–210 [Google Scholar]
  41. Kamstrup MR, Biskup E, Gjerdrum LM, Ralfkiaer E, Niazi O, Gniadecki R. 41.  2014. The importance of Notch signaling in peripheral T-cell lymphomas. Leuk. Lymphoma 55:639–44 [Google Scholar]
  42. Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF. 42.  et al. 2013. Gauging NOTCH1 activation in cancer using immunohistochemistry. PLOS ONE 8:e67306 [Google Scholar]
  43. Pancewicz J, Taylor JM, Datta A, Baydoun HH, Waldmann TA. 43.  et al. 2010. Notch signaling contributes to proliferation and tumor formation of human T-cell leukemia virus type 1-associated adult T-cell leukemia. PNAS 107:16619–24 [Google Scholar]
  44. Yeh CH, Bellon M, Pancewicz-Wojtkiewicz J, Nicot C. 44.  2016. Oncogenic mutations in the FBXW7 gene of adult T-cell leukemia patients. PNAS 113:6731–36 [Google Scholar]
  45. Tiemessen MM, Baert MR, Schonewille T, Brugman MH, Famili F. 45.  et al. 2012. The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell-specific tumor suppressor for development of lymphomas. PLOS Biol 10:e1001430 [Google Scholar]
  46. Aster JC, Blacklow SC. 46.  2012. Targeting the Notch pathway: twists and turns on the road to rational therapeutics. J. Clin. Oncol. 30:2418–20 [Google Scholar]
  47. Coude MM, Braun T, Berrou J, Dupont M, Bertrand S. 47.  et al. 2015. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget 6:17698–712 [Google Scholar]
  48. Roderick JE, Tesell J, Shultz LD, Brehm MA, Greiner DL. 48.  et al. 2014. c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood 123:1040–50 [Google Scholar]
  49. Stark GR, Darnell JE Jr.. 49.  2012. The JAK-STAT pathway at twenty. Immunity 36:503–14 [Google Scholar]
  50. Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C. 50.  et al. 1995. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269:81–83 [Google Scholar]
  51. Levy DE, Darnell JE Jr.. 51.  2002. Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 3:651–62 [Google Scholar]
  52. Kim E, Kim M, Woo DH, Shin Y, Shin J. 52.  et al. 2013. Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells. Cancer Cell 23:839–52 [Google Scholar]
  53. Lee H, Zhang P, Herrmann A, Yang C, Xin H. 53.  et al. 2012. Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation. PNAS 109:7765–69 [Google Scholar]
  54. Shuai K, Liu B. 54.  2005. Regulation of gene-activation pathways by PIAS proteins in the immune system. Nat. Rev. Immunol. 5:593–605 [Google Scholar]
  55. Sommer VH, Clemmensen OJ, Nielsen O, Wasik M, Lovato P. 55.  et al. 2004. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia 18:1288–95 [Google Scholar]
  56. Gupta M, Matthews J, Maurer MJ, Stenson M, Wellik LE. 56.  et al. 2013. In-vivo activation of STAT3 in angioimmunoblastic T cell lymphoma, PTCL not otherwise specified, and ALK negative anaplastic large cell lymphoma: implications for therapy. Blood 122:844 [Google Scholar]
  57. Zamo A, Chiarle R, Piva R, Howes J, Fan Y. 57.  et al. 2002. Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death. Oncogene 21:1038–47 [Google Scholar]
  58. Zhang Q, Wang HY, Wei F, Liu X, Paterson JC. 58.  et al. 2014. Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner. J. Immunol. 192:2913–19 [Google Scholar]
  59. Piccaluga PP, Rossi M, Agostinelli C, Ricci F, Gazzola A. 59.  et al. 2014. Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway. Leukemia 28:1687–97 [Google Scholar]
  60. Crescenzo R, Abate F, Lasorsa E, Tabbo F, Gaudiano M. 60.  et al. 2015. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell 27:516–32 [Google Scholar]
  61. Kucuk C, Jiang B, Hu X, Zhang W, Chan JK. 61.  et al. 2015. Activating mutations of STAT5B and STAT3 in lymphomas derived from gammadelta-T or NK cells. Nat. Commun. 6:6025 [Google Scholar]
  62. Vainchenker W, Constantinescu SN. 62.  2013. JAK/STAT signaling in hematological malignancies. Oncogene 32:2601–13 [Google Scholar]
  63. Waldmann TA, Chen J. 63.  2017. Disorders of the JAK/STAT pathway in T cell lymphoma pathogenesis: implications for immunotherapy. Annu. Rev. Immunol. 35:533–50 [Google Scholar]
  64. Ferrajoli A, Faderl S, Ravandi F, Estrov Z. 64.  2006. The JAK-STAT pathway: a therapeutic target in hematological malignancies. Curr. Cancer Drug Targets 6:671–79 [Google Scholar]
  65. Chen J, Zhang Y, Petrus MN, Xiao W, Nicolae A. 65.  et al. 2017. Cytokine receptor signaling is required for the survival of ALK- anaplastic large cell lymphoma, even in the presence of JAK1/STAT3 mutations. PNAS 114:3975–80 [Google Scholar]
  66. Koo GC, Tan SY, Tang T, Poon SL, Allen GE. 66.  et al. 2012. Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov 2:591–97 [Google Scholar]
  67. Bouchekioua A, Scourzic L, de Wever O, Zhang Y, Cervera P. 67.  et al. 2014. JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma. Leukemia 28:338–48 [Google Scholar]
  68. Jiang L, Gu ZH, Yan ZX, Zhao X, Xie YY. 68.  et al. 2015. Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma. Nat. Genet. 47:1061–66 [Google Scholar]
  69. Jerez A, Clemente MJ, Makishima H, Rajala H, Gomez-Segui I. 69.  et al. 2013. STAT3 mutations indicate the presence of subclinical T-cell clones in a subset of aplastic anemia and myelodysplastic syndrome patients. Blood 122:2453–59 [Google Scholar]
  70. Fasan A, Kern W, Grossmann V, Haferlach C, Haferlach T, Schnittger S. 70.  2013. STAT3 mutations are highly specific for large granular lymphocytic leukemia. Leukemia 27:1598–600 [Google Scholar]
  71. Ohgami RS, Ma L, Merker JD, Martinez B, Zehnder JL, Arber DA. 71.  2013. STAT3 mutations are frequent in CD30+ T-cell lymphomas and T-cell large granular lymphocytic leukemia. Leukemia 27:2244–47 [Google Scholar]
  72. Nicolae A, Xi L, Pham TH, Pham TA, Navarro W. 72.  et al. 2016. Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia 30:2245–47 [Google Scholar]
  73. Kiel MJ, Velusamy T, Rolland D, Sahasrabuddhe AA, Chung F. 73.  et al. 2014. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood 124:1460–72 [Google Scholar]
  74. Bellanger D, Jacquemin V, Chopin M, Pierron G, Bernard OA. 74.  et al. 2014. Recurrent JAK1 and JAK3 somatic mutations in T-cell prolymphocytic leukemia. Leukemia 28:417–19 [Google Scholar]
  75. Nairismagi ML, Tan J, Lim JQ, Nagarajan S, Ng CC. 75.  et al. 2016. JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. Leukemia 30:1311–19 [Google Scholar]
  76. Tabbo F, Barreca A, Piva R, Inghirami G. 76.  2012. ALK signaling and target therapy in anaplastic large cell lymphoma. Front. Oncol. 2:41 [Google Scholar]
  77. Adelaide J, Perot C, Gelsi-Boyer V, Pautas C, Murati A. 77.  et al. 2006. A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma. Leukemia 20:536–37 [Google Scholar]
  78. Velusamy T, Kiel MJ, Sahasrabuddhe AA, Rolland D, Dixon CA. 78.  et al. 2014. A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders. Blood 124:3768–71 [Google Scholar]
  79. Boddicker RL, Razidlo GL, Dasari S, Zeng Y, Hu G. 79.  et al. 2016. Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma. Blood 128:1234–45 [Google Scholar]
  80. Scarfo I, Pellegrino E, Mereu E, Kwee I, Agnelli L. 80.  et al. 2016. Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts. Blood 127:221–32 [Google Scholar]
  81. Pike KA, Tremblay ML. 81.  2016. TC-PTP and PTP1B: regulating JAK-STAT signaling, controlling lymphoid malignancies. Cytokine 82:52–57 [Google Scholar]
  82. Zhang Q, Raghunath PN, Xue L, Majewski M, Carpentieri DF. 82.  et al. 2002. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma. J. Immunol. 168:466–74 [Google Scholar]
  83. Ehrentraut S, Schneider B, Nagel S, Pommerenke C, Quentmeier H. 83.  et al. 2016. Th17 cytokine differentiation and loss of plasticity after SOCS1 inactivation in a cutaneous T-cell lymphoma. Oncotarget 7:34201–16 [Google Scholar]
  84. Roncero AM, Lopez-Nieva P, Cobos-Fernandez MA, Villa-Morales M, Gonzalez-Sanchez L. 84.  et al. 2016. Contribution of JAK2 mutations to T-cell lymphoblastic lymphoma development. Leukemia 30:94–103 [Google Scholar]
  85. Hanna S, El-Sibai M. 85.  2013. Signaling networks of Rho GTPases in cell motility. Cell. Signal. 25:1955–61 [Google Scholar]
  86. Bustelo XR. 86.  2014. Vav family exchange factors: an integrated regulatory and functional view. Small GTPases 5:e973757 [Google Scholar]
  87. Sahai E, Marshall CJ. 87.  2002. RHO-GTPases and cancer. Nat. Rev. Cancer 2:133–42 [Google Scholar]
  88. Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A. 88.  et al. 2014. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat. Genet. 46:166–70 [Google Scholar]
  89. Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R. 89.  et al. 2014. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat. Genet. 46:171–75 [Google Scholar]
  90. Nagata Y, Kontani K, Enami T, Kataoka K, Ishii R. 90.  et al. 2016. Variegated RHOA mutations in adult T-cell leukemia/lymphoma. Blood 127:596–604 [Google Scholar]
  91. Abate F, da Silva-Almeida AC, Zairis S, Robles-Valero J, Couronne L. 91.  et al. 2017. Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas. PNAS 114:764–69 [Google Scholar]
  92. Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T. 92.  et al. 2015. Integrated molecular analysis of adult T cell leukemia/lymphoma. Nat. Genet. 47:1304–15 [Google Scholar]
  93. Newton RH, Turka LA. 93.  2012. Regulation of T cell homeostasis and responses by pten. Front. Immunol. 3:151 [Google Scholar]
  94. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H. 94.  et al. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–35 [Google Scholar]
  95. Chen Q, Chen Y, Bian C, Fujiki R, Yu X. 95.  2013. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature 493:561–64 [Google Scholar]
  96. Deplus R, Delatte B, Schwinn MK, Defrance M, Mendez J. 96.  et al. 2013. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J 32:645–55 [Google Scholar]
  97. Yang L, Rau R, Goodell MA. 97.  2015. DNMT3A in haematological malignancies. Nat. Rev. Cancer 15:152–65 [Google Scholar]
  98. Zhang W, Xu J. 98.  2017. DNA methyltransferases and their roles in tumorigenesis. Biomark. Res. 5:1 [Google Scholar]
  99. Jeong M, Sun D, Luo M, Huang Y, Challen GA. 99.  et al. 2014. Large conserved domains of low DNA methylation maintained by Dnmt3a. Nat. Genet. 46:17–23 [Google Scholar]
  100. Nguyen TB, Sakata-Yanagimoto M, Asabe Y, Matsubara D, Kano J. 100.  et al. 2017. Identification of cell-type-specific mutations in nodal T-cell lymphomas. Blood Cancer J 7:e516 [Google Scholar]
  101. Wang C, McKeithan TW, Gong Q, Zhang W, Bouska A. 101.  et al. 2015. IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood 126:1741–52 [Google Scholar]
  102. Odejide O, Weigert O, Lane AA, Toscano D, Lunning MA. 102.  et al. 2014. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood 123:1293–96 [Google Scholar]
  103. Russler-Germain DA, Spencer DH, Young MA, Lamprecht TL, Miller CA. 103.  et al. 2014. The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 25:442–54 [Google Scholar]
  104. Haney SL, Upchurch GM, Opavska J, Klinkebiel D, Hlady RA. 104.  et al. 2016. Dnmt3a is a haploinsufficient tumor suppressor in CD8+ peripheral T cell lymphoma. PLOS Genet 12:e1006334 [Google Scholar]
  105. Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L. 105.  et al. 2012. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood 119:1901–3 [Google Scholar]
  106. Greenberg ME, Ziff EB. 106.  1984. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311:433–38 [Google Scholar]
  107. Shaulian E, Karin M. 107.  2002. AP-1 as a regulator of cell life and death. Nat. Cell Biol. 4:E131–36 [Google Scholar]
  108. Matsuoka M, Jeang KT. 108.  2007. Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat. Rev. Cancer 7:270–80 [Google Scholar]
  109. Macaire H, Riquet A, Moncollin V, Biemont-Trescol MC, Duc Dodon M. 109.  et al. 2012. Tax protein-induced expression of antiapoptotic Bfl-1 protein contributes to survival of human T-cell leukemia virus type 1 (HTLV-1)-infected T-cells. J. Biol. Chem. 287:21357–70 [Google Scholar]
  110. Laimer D, Dolznig H, Kollmann K, Vesely PW, Schlederer M. 110.  et al. 2012. PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nat. Med. 18:1699–704 [Google Scholar]
  111. Schiefer AI, Vesely P, Hassler MR, Egger G, Kenner L. 111.  2015. The role of AP-1 and epigenetics in ALCL. Front. Biosci. 7:226–35 [Google Scholar]
  112. Watatani Y, Sato Y, Nishikawa K, Miyachi H, Shiraishi Y. 112.  et al. 2016. Molecular heterogeneity in peripheral T-cell lymphoma not otherwise specified revealed by comprehensive mutational profiling. Blood 128:2927 [Google Scholar]
  113. Nickoloff BJ, Nestle FO, Zheng XG, Turka LA. 113.  1994. T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28. Blood 83:2580–86 [Google Scholar]
  114. Hasegawa H, Yamada Y, Harasawa H, Tsuji T, Murata K. 114.  et al. 2005. Sensitivity of adult T-cell leukaemia lymphoma cells to tumour necrosis factor-related apoptosis-inducing ligand. Br. J. Haematol. 128:253–65 [Google Scholar]
  115. Zheng Z, Cheng S, Wu W, Wang L, Zhao Y. 115.  et al. 2014. c-FLIP is involved in tumor progression of peripheral T-cell lymphoma and targeted by histone deacetylase inhibitors. J. Hematol. Oncol. 7:88 [Google Scholar]
  116. de Leval L, Rickman DS, Thielen C, Reynies A, Huang YL. 116.  et al. 2007. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood 109:4952–63 [Google Scholar]
  117. Cai Q, Huang H-Q, Bai B, Yan G, Li S. 117.  et al. 2013. The serum spectrum of cytokines in patients with NK/T-cell lymphoma and its clinical significance in survival. Blood 122:1759 [Google Scholar]
  118. Sakaguchi S. 118.  2004. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22:531–62 [Google Scholar]
  119. Wang J, Ke XY. 119.  2011. The four types of Tregs in malignant lymphomas. J. Hematol. Oncol. 4:50 [Google Scholar]
  120. Kim WY, Jeon YK, Kim TM, Kim JE, Kim YA. 120.  et al. 2009. Increased quantity of tumor-infiltrating FOXP3-positive regulatory T cells is an independent predictor for improved clinical outcome in extranodal NK/T-cell lymphoma. Ann. Oncol. 20:1688–96 [Google Scholar]
  121. Kasprzycka M, Marzec M, Liu X, Zhang Q, Wasik MA. 121.  2006. Nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) oncoprotein induces the T regulatory cell phenotype by activating STAT3. PNAS 103:9964–69 [Google Scholar]
  122. Karwacz K, Bricogne C, MacDonald D, Arce F, Bennett CL. 122.  et al. 2011. PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells. EMBO Mol. Med. 3:581–92 [Google Scholar]
  123. Wilcox RA, Feldman AL, Wada DA, Yang ZZ, Comfere NI. 123.  et al. 2009. B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood 114:2149–58 [Google Scholar]
  124. Jo JC, Kim M, Choi Y, Kim HJ, Kim JE. 124.  et al. 2017. Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type. Ann. Hematol. 96:25–31 [Google Scholar]
  125. Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A. 125.  et al. 2016. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J. Clin. Oncol. 34:2698–704 [Google Scholar]
  126. Chanmee T, Ontong P, Konno K, Itano N. 126.  2014. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers 13:1670–90 [Google Scholar]
  127. Lin ZX, Bai B, Cai QC, Cai QQ, Wang XX. 127.  et al. 2012. High numbers of tumor-associated macrophages correlate with poor prognosis in patients with mature T- and natural killer cell lymphomas. Med. Oncol. 29:3522–28 [Google Scholar]
  128. Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. 128.  2013. Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 229:176–85 [Google Scholar]
  129. Zhao WL, Mourah S, Mounier N, Leboeuf C, Daneshpouy ME. 129.  et al. 2004. Vascular endothelial growth factor-A is expressed both on lymphoma cells and endothelial cells in angioimmunoblastic T-cell lymphoma and related to lymphoma progression. Lab. Invest. 84:1512–19 [Google Scholar]
  130. Tabiasco J, Vercellone A, Meggetto F, Hudrisier D, Brousset P, Fournie JJ. 130.  2003. Acquisition of viral receptor by NK cells through immunological synapse. J. Immunol. 170:5993–98 [Google Scholar]
  131. Chen J. 131.  2012. Roles of the PI3K/Akt pathway in Epstein-Barr virus-induced cancers and therapeutic implications. World J. Virol. 1:154–61 [Google Scholar]
  132. Young LS, Rickinson AB. 132.  2004. Epstein-Barr virus: 40 years on. Nat. Rev. Cancer 4:757–68 [Google Scholar]
  133. Piccaluga PP, Gazzola A, Agostinelli C, Bacci F, Sabattini E, Pileri SA. 133.  2011. Pathobiology of Epstein-Barr virus-driven peripheral T-cell lymphomas. Semin. Diagn. Pathol. 28:234–44 [Google Scholar]
  134. Rowe M, Raithatha S, Shannon-Lowe C. 134.  2014. Counteracting effects of cellular Notch and Epstein-Barr virus EBNA2: implications for stromal effects on virus-host interactions. J. Virol. 88:2012065–76 [Google Scholar]
  135. Miyauchi K, Urano E, Yoshiyama H, Komano J. 135.  2011. Cytokine signatures of transformed B cells with distinct Epstein-Barr virus latencies as a potential diagnostic tool for B cell lymphoma. Cancer Sci 102:1236–41 [Google Scholar]
  136. Takahara M, Kis LL, Nagy N, Liu A, Harabuchi Y. 136.  et al. 2006. Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3. Int. J. Cancer 119:2775–83 [Google Scholar]
  137. Green MR, Rodig S, Juszczynski P, Ouyang J, Sinha P. 137.  et al. 2012. Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin. Cancer Res. 18:1611–18 [Google Scholar]
  138. Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG. 138.  et al. 2013. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin. Cancer Res. 19:3462–73 [Google Scholar]
  139. Nagato T, Ohkuri T, Ohara K, Hirata Y, Kishibe K. 139.  et al. 2017. Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Cancer Immunol. Immunother. 66:877–90 [Google Scholar]
  140. Gallo RC. 140.  2011. Research and discovery of the first human cancer virus, HTLV-1. Best Pract. Res. Clin. Haematol. 24:559–65 [Google Scholar]
  141. Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L. 141.  2008. The HTLV-1 Tax interactome. Retrovirology 5:76 [Google Scholar]
  142. Grassmann R, Aboud M, Jeang KT. 142.  2005. Molecular mechanisms of cellular transformation by HTLV-1 Tax. Oncogene 24:5976–85 [Google Scholar]
  143. Ma G, Yasunaga J, Matsuoka M. 143.  2016. Multifaceted functions and roles of HBZ in HTLV-1 pathogenesis. Retrovirology 13:16 [Google Scholar]
  144. Philip S, Zahoor MA, Zhi H, Ho YK, Giam CZ. 144.  2014. Regulation of human T-lymphotropic virus type I latency and reactivation by HBZ and Rex. PLOS Pathog 10:e1004040 [Google Scholar]
  145. Polakowski N, Terol M, Hoang K, Nash I, Laverdure S. 145.  et al. 2014. HBZ stimulates brain-derived neurotrophic factor/TrkB autocrine/paracrine signaling to promote survival of human T-cell leukemia virus type 1-infected T cells. J. Virol. 88:13482–94 [Google Scholar]
  146. Wright DG, Marchal C, Hoang K, Ankney JA, Nguyen ST. 146.  et al. 2016. Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1. Oncotarget 7:1687–706 [Google Scholar]
  147. Borowiak M, Kuhlmann AS, Girard S, Gazzolo L, Mesnard JM. 147.  et al. 2013. HTLV-1 bZIP factor impedes the menin tumor suppressor and upregulates JunD-mediated transcription of the hTERT gene. Carcinogenesis 34:2664–72 [Google Scholar]
  148. Zhao T, Matsuoka M. 148.  2012. HBZ and its roles in HTLV-1 oncogenesis. Front. Microbiol. 3:247 [Google Scholar]
  149. Nakayama T, Hieshima K, Arao T, Jin Z, Nagakubo D. 149.  et al. 2008. Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia. Oncogene 27:3221–32 [Google Scholar]
  150. Ma H, Abdul-Hay M. 150.  2017. T-cell lymphomas, a challenging disease: types, treatments, and future. Int. J. Clin. Oncol. 22:18–51 [Google Scholar]
/content/journals/10.1146/annurev-pathol-020117-043821
Loading
/content/journals/10.1146/annurev-pathol-020117-043821
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error