1932

Abstract

Lymphomas represent clonal proliferations of lymphocytes that are broadly classified based upon their maturity (peripheral or mature versus precursor) and lineage (B cell, T cell, and natural killer cell). Insights into the pathogenetic mechanisms involved in lymphoma impact the classification of lymphoma and have significant implications for the diagnosis and clinical management of patients. Serial scientific and technologic advances over the last 30 years in immunology, cytogenetics, molecular biology, gene expression profiling, mass spectrometry–based proteomics, and, more recently, next-generation sequencing have contributed to greatly enhance our understanding of the pathogenetic mechanisms in lymphoma. Novel and emerging concepts that challenge our previously accepted paradigms about lymphoma biology and how these impact diagnosis, molecular testing, disease monitoring, drug development, and personalized and precision medicine for lymphoma are discussed.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-020117-043803
2018-01-24
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/pathol/13/1/annurev-pathol-020117-043803.html?itemId=/content/journals/10.1146/annurev-pathol-020117-043803&mimeType=html&fmt=ahah

Literature Cited

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA. 1.  et al. 2008. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues Lyon, France: Int. Agency Res. Cancer
  2. Jaffe ES, Arber DA, Campo E, Harris NL, Quintanilla-Fend L. 2. , eds. 2017. Hematopathology Philadelphia: Elsevier, 2nd ed..
  3. Koues OI, Kowalewski RA, Chang LW, Pyfrom SC, Schmidt JA. 3.  et al. 2015. Enhancer sequence variants and transcription-factor deregulation synergize to construct pathogenic regulatory circuits in B-cell lymphoma. Immunity 42:186–98 [Google Scholar]
  4. Chapuy B, McKeown MR, Lin CY, Monti S, Roemer MG. 4.  et al. 2013. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell 24:777–90 [Google Scholar]
  5. Amarnath S, Mangus CW, Wang JC, Wei F, He A. 5.  et al. 2011. The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci. Transl. Med. 3:111ra20 [Google Scholar]
  6. Easterfield AJ, Bradley JA, Bolton EM. 6.  2003. Complementary DNA sequences encoding the rat MHC class II RT1-Bu and RT1-Du α and β chains. Immunogenetics 55:344–50 [Google Scholar]
  7. Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G. 7.  et al. 2011. Combined genetic inactivation of β2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell 20:728–40 [Google Scholar]
  8. Schneider M, Schneider S, Zuhlke-Jenisch R, Klapper W, Sundstrom C. 8.  et al. 2015. Alterations of the CD58 gene in classical Hodgkin lymphoma. Genes Chromosomes Cancer 54:638–45 [Google Scholar]
  9. Casey SC, Tong L, Li Y, Do R, Walz S. 9.  et al. 2016. MYC regulates the antitumor immune response through CD47 and PD-L1. Science 352:227–31 [Google Scholar]
  10. Marzec M, Zhang Q, Goradia A, Raghunath PN, Liu X. 10.  et al. 2008. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). PNAS 105:20852–57 [Google Scholar]
  11. Voena C, Menotti M, Mastini C, Di Giacomo F, Longo DL. 11.  et al. 2015. Efficacy of a cancer vaccine against ALK-rearranged lung tumors. Cancer Immunol. Res. 3:1333–43 [Google Scholar]
  12. Yamamoto R, Nishikori M, Tashima M, Sakai T, Ichinohe T. 12.  et al. 2009. B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma. Cancer Sci 100:2093–100 [Google Scholar]
  13. Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M. 13.  et al. 2011. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature 471:377–81 [Google Scholar]
  14. Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T. 14.  et al. 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 116:3268–77 [Google Scholar]
  15. Twa DD, Chan FC, Ben-Neriah S, Woolcock BW, Mottok A. 15.  et al. 2014. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood 123:2062–65 [Google Scholar]
  16. Van Roosbroeck K, Ferreiro JF, Tousseyn T, van der Krogt JA, Michaux L. 16.  et al. 2016. Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies. Genes Chromosomes Cancer 55:428–41 [Google Scholar]
  17. Chong L, Twa D, Mottok A, Ben-Neriah S, Woolcock W. 17.  et al. 2016. Comprehensive characterization of programmed death ligand structural rearrangements in B cell non-Hodgkin lymphomas. Blood 128:1206–13 [Google Scholar]
  18. Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA. 18.  et al. 2016. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J. Clin. Oncol. 34:2690–97 [Google Scholar]
  19. Greaves P, Gribben JG. 19.  2013. The role of B7 family molecules in hematologic malignancy. Blood 121:734–44 [Google Scholar]
  20. Kataoka K, Shiraishi Y, Takeda Y, Sakata S, Matsumoto M. 20.  et al. 2016. Aberrant PD-L1 expression through 3′ UTR disruption in multiple cancers. Nature 534:402–6 [Google Scholar]
  21. Swerdlow SH. 21. , Int. Agency Res. Cancer, World Health Organ. 2008. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues Lyon, France: Int. Agency Res. Cancer
  22. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS. 22.  et al. 2000. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–11 [Google Scholar]
  23. Rosenwald A, Wright G, Leroy K, Yu X, Gaulard P. 23.  et al. 2003. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J. Exp. Med. 198:851–62 [Google Scholar]
  24. Davis RE, Ngo VN, Lenz G, Tolar P, Young RM. 24.  et al. 2010. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463:88–92 [Google Scholar]
  25. Xu Y, Harder KW, Huntington ND, Hibbs ML, Tarlinton DM. 25.  2005. Lyn tyrosine kinase: accentuating the positive and the negative. Immunity 22:9–18 [Google Scholar]
  26. Battistella M, Romero M, Castro-Vega LJ, Gapihan G, Bouhidel F. 26.  et al. 2015. The high expression of the microRNA 17–92 cluster and its paralogs, and the downregulation of the target gene PTEN, is associated with primary cutaneous B-cell lymphoma progression. J. Investig. Dermatol. 135:1659–67 [Google Scholar]
  27. Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A. 27.  et al. 2011. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 471:189–95 [Google Scholar]
  28. Steidl C, Gascoyne RD. 28.  2011. The molecular pathogenesis of primary mediastinal large B-cell lymphoma. Blood 118:2659–69 [Google Scholar]
  29. Young RM, Shaffer AL 3rd, Phelan JD, Staudt LM. 29.  2015. B-cell receptor signaling in diffuse large B-cell lymphoma. Semin. Hematol. 52:77–85 [Google Scholar]
  30. Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S. 30.  et al. 2015. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat. Med. 21:922–26 [Google Scholar]
  31. Naylor TL, Tang H, Ratsch BA, Enns A, Loo A. 31.  et al. 2011. Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas. Cancer Res 71:2643–53 [Google Scholar]
  32. Zhang LH, Kosek J, Wang M, Heise C, Schafer PH, Chopra R. 32.  2013. Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF4 and cereblon expression. Br. J. Haematol. 160:487–502 [Google Scholar]
  33. Garcia PD, Langowski JL, Wang Y, Chen M, Castillo J. 33.  et al. 2014. Pan-PIM kinase inhibition provides a novel therapy for treating hematologic cancers. Clin. Cancer Res. 20:1834–45 [Google Scholar]
  34. Bradley WD, Arora S, Busby J, Balasubramanian S, Gehling VS. 34.  et al. 2014. EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation. Chem. Biol. 21:1463–75 [Google Scholar]
  35. Boddicker R, Razidlo G, Dasari S, Zeng Y, Hu G. 35.  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]
  36. Vallois D, Dobay MP, Morin RD, Lemonnier F, Missiaglia E. 36.  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]
  37. Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T. 37.  et al. 2015. Integrated molecular analysis of adult T cell leukemia/lymphoma. Nat. Genet. 47:1304–15 [Google Scholar]
  38. Nakagawa M, Schmitz R, Xiao W, Goldman CK, Xu W. 38.  et al. 2014. Gain-of-function CCR4 mutations in adult T cell leukemia/lymphoma. J. Exp. Med. 211:2497–505 [Google Scholar]
  39. Boddicker RL, Razidlo GL, Feldman AL. 39.  2016. Genetic alterations affecting GTPases and T-cell receptor signaling in peripheral T-cell lymphomas. Small GTPases In press. https://doi.org/10.1080/21541248.2016.1263718 [Crossref]
  40. Chiba S, Enami T, Ogawa S, Sakata-Yanagimoto M. 40.  2015. G17V RHOA: genetic evidence of GTP-unbound RHOA playing a role in tumorigenesis in T cells. Small GTPases 6:100–3 [Google Scholar]
  41. Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R. 41.  et al. 2014. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat. Genet. 46:171–75 [Google Scholar]
  42. Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A. 42.  et al. 2014. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat. Genet. 46:166–70 [Google Scholar]
  43. Abate F, da Silva-Almeida AC, Zairis S, Robles-Valero J, Couronne L. 43.  et al. 2017. Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas. PNAS 114:764–69 [Google Scholar]
  44. Matutes E, Brito-Babapulle V, Swansbury J, Ellis J, Morilla R. 44.  et al. 1991. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 78:3269–74 [Google Scholar]
  45. Hopfinger G, Busch R, Pflug N, Weit N, Westermann A. 45.  et al. 2013. Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia. Cancer 119:2258–67 [Google Scholar]
  46. Virgilio L, Narducci MG, Isobe M, Billips LG, Cooper MD. 46.  et al. 1994. Identification of the TCL1 gene involved in T-cell malignancies. PNAS 91:12530–34 [Google Scholar]
  47. Pekarsky Y, Hallas C, Isobe M, Russo G, Croce CM. 47.  1999. Abnormalities at 14q32.1 in T cell malignancies involve two oncogenes. PNAS 96:2949–51 [Google Scholar]
  48. Stern MH, Soulier J, Rosenzwajg M, Nakahara K, Canki-Klain N. 48.  et al. 1993. MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations. Oncogene 8:2475–83 [Google Scholar]
  49. Kiel MJ, Velusamy T, Rolland D, Sahasrabuddhe AA, Chung F. 49.  et al. 2014. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood 124:1460–72 [Google Scholar]
  50. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R. 50.  et al. 2005. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med. 352:1779–90 [Google Scholar]
  51. Elliott NE, Cleveland SM, Grann V, Janik J, Waldmann TA, Davé UP. 51.  2011. FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma. Blood 118:3911–21 [Google Scholar]
  52. Jerez A, Clemente MJ, Makishima H, Koskela H, Leblanc F. 52.  et al. 2012. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood 120:3048–57 [Google Scholar]
  53. Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmaki H. 53.  et al. 2012. Somatic STAT3 mutations in large granular lymphocytic leukemia. N. Engl. J. Med. 366:1905–13 [Google Scholar]
  54. Jerez A, Clemente MJ, Makishima H, Rajala H, Gomez-Segui I. 54.  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]
  55. Rajala HL, Eldfors S, Kuusanmaki H, van Adrichem AJ, Olson T. 55.  et al. 2013. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood 121:4541–50 [Google Scholar]
  56. Kucuk C, Jiang B, Hu X, Zhang W, Chan JK. 56.  et al. 2015. Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells. Nat. Commun. 6:6025 [Google Scholar]
  57. Ohgami RS, Ma L, Merker JD, Martinez B, Zehnder JL, Arber DA. 57.  2013. STAT3 mutations are frequent in CD30+ T-cell lymphomas and T-cell large granular lymphocytic leukemia. Leukemia 27:2244–47 [Google Scholar]
  58. McKinney M, Moffitt AB, Gaulard P, Travert M, De Leval L. 58.  et al. 2017. The genetic basis of hepatosplenic T-cell lymphoma. Cancer Discov 7:369–79 [Google Scholar]
  59. Andersson EI, Tanahashi T, Sekiguchi N, Gasparini VR, Bortoluzzi S. 59.  et al. 2016. High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. Blood 128:2465–68 [Google Scholar]
  60. Roberti A, Dobay MP, Bisig B, Vallois D, Boechat C. 60.  et al. 2016. Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat. Commun. 7:12602 [Google Scholar]
  61. Choi J, Goh G, Walradt T, Hong BS, Bunick CG. 61.  et al. 2015. Genomic landscape of cutaneous T cell lymphoma. Nat. Genet. 47:91011–19 [Google Scholar]
  62. Kiel MJ, Sahasrabuddhe AA, Rolland DCM, Velusamy T, Chung F. 62.  et al. 2015. Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK-STAT pathway in Sézary syndrome. Nat. Commun. 6:8470 [Google Scholar]
  63. Park J, Yang J, Wenzel AT, Ramachandran A, Lee WJ. 63.  et al. 2017. Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p.Q575E). Blood 130:1430–40 [Google Scholar]
  64. Lettice LA, Daniels S, Sweeney E, Venkataraman S, Devenney PS. 64.  et al. 2011. Enhancer-adoption as a mechanism of human developmental disease. Hum. Mutat. 32:1492–99 [Google Scholar]
  65. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V. 65.  et al. 2013. Super-enhancers in the control of cell identity and disease. Cell 155:934–47 [Google Scholar]
  66. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW. 66.  et al. 2007. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39:311–18 [Google Scholar]
  67. Sur I, Taipale J. 67.  2016. The role of enhancers in cancer. Nat. Rev. Cancer 16:483–93 [Google Scholar]
  68. Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J. 68.  et al. 2014. An atlas of active enhancers across human cell types and tissues. Nature 507:455–61 [Google Scholar]
  69. Ryan RJ, Drier Y, Whitton H, Cotton MJ, Kaur J. 69.  et al. 2015. Detection of enhancer-associated rearrangements reveals mechanisms of oncogene dysregulation in B-cell lymphoma. Cancer Discov 5:1058–71 [Google Scholar]
  70. Jiang Y, Ortega-Molina A, Geng H, Ying HY, Hatzi K. 70.  et al. 2017. CREBBP inactivation promotes the development of HDAC3-dependent lymphomas. Cancer Discov 7:38–53 [Google Scholar]
  71. Zhang J, Vlasevska S, Wells VA, Nataraj S, Holmes AB. 71.  et al. 2017. The CREBBP acetyltransferase is a haploinsufficient tumor suppressor in B cell lymphoma. Cancer Discov 7:322–37 [Google Scholar]
  72. Chapuy B, McKeown MR, Lin CY, Monti S, Roemer MGM. 72.  et al. 2013. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell 24:6777–90 [Google Scholar]
  73. Loven J, Hoke HA, Lin CY, Lau A, Orlando DA. 73.  et al. 2013. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153:320–34 [Google Scholar]
  74. Bradner JE, Hnisz D, Young RA. 74.  2017. Transcriptional addiction in cancer. Cell 168:629–43 [Google Scholar]
  75. Biamonti G, Catillo M, Pignataro D, Montecucco A, Ghigna C. 75.  2014. The alternative splicing side of cancer. Semin. Cell Dev. Biol. 32:30–36 [Google Scholar]
  76. Wahl MC, Will CL, Luhrmann R. 76.  2009. The spliceosome: design principles of a dynamic RNP machine. Cell 136:701–18 [Google Scholar]
  77. Padgett RA. 77.  2012. New connections between splicing and human disease. Trends Genet 28:147–54 [Google Scholar]
  78. Quesada V, Conde L, Villamor N, Ordonez GR, Jares P. 78.  et al. 2011. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat. Genet. 44:47–52 [Google Scholar]
  79. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C. 79.  et al. 2011. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N. Engl. J. Med. 365:2497–506 [Google Scholar]
  80. Rossi D, Bruscaggin A, Spina V, Rasi S, Khiabanian H. 80.  et al. 2011. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 118:6904–8 [Google Scholar]
  81. Isono K, Mizutani-Koseki Y, Komori T, Schmidt-Zachmann MS, Koseki H. 81.  2005. Mammalian Polycomb-mediated repression of Hox genes requires the essential spliceosomal protein Sf3b1. Genes Dev 19:536–41 [Google Scholar]
  82. Hsu TY, Simon LM, Neill NJ, Marcotte R, Sayad A. 82.  et al. 2015. The spliceosome is a therapeutic vulnerability in MYC-driven cancer. Nature 525:384–88 [Google Scholar]
  83. Polprasert C, Schulze I, Sekeres MA, Makishima H, Przychodzen B. 83.  et al. 2015. Inherited and somatic defects in DDX41 in myeloid neoplasms. Cancer Cell 27:658–70 [Google Scholar]
  84. Lewinsohn M, Brown AL, Weinel LM, Phung C, Rafidi G. 84.  et al. 2016. Novel germ line DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies. Blood 127:1017–23 [Google Scholar]
  85. Bonnal S, Vigevani L, Valcarcel J. 85.  2012. The spliceosome as a target of novel antitumour drugs. Nat. Rev. Drug Discov. 11:847–59 [Google Scholar]
  86. Webb TR, Joyner AS, Potter PM. 86.  2013. The development and application of small molecule modulators of SF3b as therapeutic agents for cancer. Drug Discov. Today 18:43–49 [Google Scholar]
  87. Zhou J, Chng WJ. 87.  2017. Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia. Stem Cell Investig 4:6 [Google Scholar]
  88. Brown PJ, Ashe SL, Leich E, Burek C, Barrans S. 88.  et al. 2008. Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL. Blood 111:2816–24 [Google Scholar]
  89. Nakayama K, Nagahama H, Minamishima YA, Miyake S, Ishida N. 89.  et al. 2004. Skp2-mediated degradation of p27 regulates progression into mitosis. Dev. Cell 6:661–72 [Google Scholar]
  90. Orian A, Gonen H, Bercovich B, Fajerman I, Eytan E. 90.  et al. 2000. SCFβ-TrCP ubiquitin ligase-mediated processing of NF-κB p105 requires phosphorylation of its C-terminus by IκB kinase. EMBO J 19:2580–91 [Google Scholar]
  91. Santra MK, Wajapeyee N, Green MR. 91.  2009. F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature 459:722–25 [Google Scholar]
  92. Liu J, Wan L, Liu P, Inuzuka H, Liu J. 92.  et al. 2014. SCFβ-TrCP-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway. Oncotarget 5:1026–37 [Google Scholar]
  93. Schneider C, Kon N, Amadori L, Shen Q, Schwartz FH. 93.  et al. 2016. FBXO11 inactivation leads to abnormal germinal-center formation and lymphoproliferative disease. Blood 128:660–66 [Google Scholar]
  94. Busino L, Millman SE, Scotto L, Kyratsous CA, Basrur V. 94.  et al. 2012. Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nat. Cell Biol. 14:375–85 [Google Scholar]
  95. Amir RE, Haecker H, Karin M, Ciechanover A. 95.  2004. Mechanism of processing of the NF-κB2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCFβ-TrCP ubiquitin ligase. Oncogene 23:2540–47 [Google Scholar]
  96. Busino L, Millman SE, Pagano M. 96.  2012. SCF-mediated degradation of p100 (NF-κB2): mechanisms and relevance in multiple myeloma. Sci. Signal. 5:pt14 [Google Scholar]
  97. Welcker M, Orian A, Jin JP, Grim JA, Harper JW. 97.  et al. 2004. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. PNAS 101:9085–90 [Google Scholar]
  98. Sahasrabuddhe AA, Elenitoba-Johnson KS. 98.  2015. The role of aberrant proteolysis in lymphomagenesis. Curr. Opin. Hematol. 22:369–78 [Google Scholar]
  99. Sahasrabuddhe AA, Elenitoba-Johnson KS. 99.  2015. Role of the ubiquitin proteasome system in hematologic malignancies. Immunol. Rev. 263:224–39 [Google Scholar]
  100. Weng AP, Ferrando AA, Lee W, Morris JPT, Silverman LB. 100.  et al. 2004. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306:269–71 [Google Scholar]
  101. Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG. 101.  et al. 2012. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J. Exp. Med. 209:1553–65 [Google Scholar]
  102. Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR. 102.  et al. 2011. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 475:101–5 [Google Scholar]
  103. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J. 103.  et al. 2010. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat. Genet. 42:181–85 [Google Scholar]
  104. Beguelin W, Popovic R, Teater M, Jiang Y, Bunting KL. 104.  et al. 2013. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell 23:677–92 [Google Scholar]
  105. Sahasrabuddhe AA, Chen X, Chung F, Velusamy T, Lim MS, Elenitoba-Johnson KS. 105.  2015. Oncogenic Y641 mutations in EZH2 prevent Jak2/β-TrCP-mediated degradation. Oncogene 34:445–54 [Google Scholar]
  106. Rosebeck S, Madden L, Jin X, Gu S, Apel IJ. 106.  et al. 2011. Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-κB activation. Science 331:468–72 [Google Scholar]
  107. Nie Z, Du MQ, McAllister-Lucas LM, Lucas PC, Bailey NG. 107.  et al. 2015. Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2-MALT1 in MALT lymphoma. Nat. Commun. 6:5908 [Google Scholar]
  108. Rosebeck S, Lim MS, Elenitoba-Johnson KS, McAllister-Lucas LM, Lucas PC. 108.  2016. API2-MALT1 oncoprotein promotes lymphomagenesis via unique program of substrate ubiquitination and proteolysis. World J. Biol. Chem. 7:128–37 [Google Scholar]
  109. Fischer ES, Bohm K, Lydeard JR, Yang H, Stadler MB. 109.  et al. 2014. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512:49–53 [Google Scholar]
  110. Gopalakrishnan R, Matta H, Tolani B, Triche T Jr., Chaudhary PM. 110.  2016. Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors. Oncogene 35:1797–810 [Google Scholar]
  111. Gribben JG, Fowler N, Morschhauser F. 111.  2015. Mechanisms of action of lenalidomide in B-cell non-Hodgkin lymphoma. J. Clin. Oncol. 33:2803–11 [Google Scholar]
  112. Ravi D, Beheshti A, Abermil N, Passero F, Sharma J. 112.  et al. 2016. Proteasomal inhibition by ixazomib induces CHK1 and MYC-dependent cell death in T-cell and Hodgkin lymphoma. Cancer Res 76:3319–31 [Google Scholar]
  113. Paulus A, Akhtar S, Caulfield TR, Samuel K, Yousaf H. 113.  et al. 2016. Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells. Blood Cancer J 6:e492 [Google Scholar]
  114. Hanahan D, Weinberg RA. 114.  2011. Hallmarks of cancer: the next generation. Cell 144:646–74 [Google Scholar]
  115. Warburg O, Wind F, Negelein E. 115.  1927. The metabolism of tumors in the body. J. Gen. Physiol. 8:519–30 [Google Scholar]
  116. Lunt SY, Vander Heiden MG. 116.  2011. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 27:441–64 [Google Scholar]
  117. Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B. 117.  et al. 2012. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 22:547–60 [Google Scholar]
  118. Muralidharan G, Micalizzi M, Speth J, Raible D, Troy S. 118.  2005. Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob. Agents Chemother. 49:220–29 [Google Scholar]
  119. Norberg E, Lako A, Chen PH, Stanley IA, Zhou F. 119.  et al. 2017. Differential contribution of the mitochondrial translation pathway to the survival of diffuse large B-cell lymphoma subsets. Cell Death Differ 24:251–62 [Google Scholar]
  120. McDonnell SR, Hwang SR, Rolland D, Murga-Zamalloa C, Basrur V. 120.  et al. 2013. Integrated phosphoproteomic and metabolomic profiling reveals NPM-ALK-mediated phosphorylation of PKM2 and metabolic reprogramming in anaplastic large cell lymphoma. Blood 122:958–68 [Google Scholar]
  121. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE. 121.  et al. 2008. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452:230–33 [Google Scholar]
  122. Shim H, Dolde C, Lewis BC, Wu CS, Dang G. 122.  et al. 1997. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. PNAS 94:6658–63 [Google Scholar]
  123. Hitosugi T, Fan J, Chung TW, Lythgoe K, Wang X. 123.  et al. 2011. Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol. Cell 44:864–77 [Google Scholar]
  124. Hitosugi T, Zhou L, Elf S, Fan J, Kang HB. 124.  et al. 2012. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell 22:585–600 [Google Scholar]
  125. Cea M, Cagnetta A, Acharya C, Acharya P, Tai YT. 125.  et al. 2016. Dual NAMPT and BTK targeting leads to synergistic killing of Waldenstrom macroglobulinemia cells regardless of MYD88 and CXCR4 somatic mutation status. Clin. Cancer Res. 22:6099–109 [Google Scholar]
  126. Martin MJ, Eberlein C, Taylor M, Ashton S, Robinson D, Cross D. 126.  2016. Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma. Oncotarget 7:86313–25 [Google Scholar]
  127. Yang F, Du J, Zhang H, Ruan G, Xiang J. 127.  et al. 2017. Serum metabolomics of Burkitt lymphoma mouse models. PLOS ONE 12:e0170896 [Google Scholar]
/content/journals/10.1146/annurev-pathol-020117-043803
Loading
/content/journals/10.1146/annurev-pathol-020117-043803
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