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Molecular Pathogenesis of Peripheral T Cell Lymphoma

  • T-Cell and Other Lymphoproliferative Malignancies (P Porcu, Section Editor)
  • Published:
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Abstract

Understanding the molecular pathogenesis of peripheral T cell lymphomas (PTCLs) has lagged behind that of B cell lymphomas due to disease rarity. However, novel approaches are gradually clarifying these mechanisms, and gene profiling has identified specific signaling pathways governing PTCL cell survival and growth. For example, genetic alterations have been discovered, including signal transducer and activator of transcription (STAT)3 and STAT5b mutations in several PTCLs, disease-specific ras homolog family member A (RHOA) mutations in angioimmunoblastic T cell lymphoma (AITL), and recurrent translocations at the dual specificity phosphatase 22 (DUSP22) locus in anaplastic lymphoma receptor tyrosine kinase (ALK)-negative anaplastic large cell lymphomas (ALCLs). Intriguingly, some PTCL-relevant mutations are seen in apparently normal blood cells as well as tumor cells, while others are confined to tumor cells. These data have dramatically changed our understanding of PTCL origins: once considered to originate from mature T lymphocytes, some PTCLs are now believed to emerge from immature hematopoietic progenitor cells.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC Press; 2008.

    Google Scholar 

  2. Sakata-Yanagimoto M. Multistep tumorigenesis in peripheral T cell lymphoma. Int J Hematol. 2015. doi:10.1007/s12185-015-1738-8.

  3. Quivoron C, Couronne L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell. 2011;20(1):25–38. TET2 mutations were firstly identified in normal blood cells in peripheral T-cell lymphoma (PTCL).

  4. Couronne L, Bastard C, Bernard OA. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012;366(1):95–6.

    Article  CAS  PubMed  Google Scholar 

  5. Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–5. Recurrent RHOA mutations were discovered in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) with AITL features. Coexistence of RHOA mutations and TET2/IDH2 mutations were identified.

  6. Iqbal J, Wright G, Wang C, Rosenwald A, Gascoyne RD, Weisenburger DD, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood. 2014;123(19):2915–23. Gene expression profiling (GEP) identified subgroups in PTCL-NOS. The GATA3 subgroup was associated with poor overall survival.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Piccaluga PP, Fuligni F, De Leo A, Bertuzzi C, Rossi M, Bacci F, et al. Molecular profiling improves classification and prognostication of nodal peripheral T-cell lymphomas: results of a phase III diagnostic accuracy study. J Clin Oncol. 2013;31(24):3019–25.

    Article  PubMed  Google Scholar 

  8. Iqbal J, Weisenburger DD, Greiner TC, Vose JM, McKeithan T, Kucuk C, et al. Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. Blood. 2010;115(5):1026–36.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Amsen D, Spilianakis CG, Flavell RA. How are T(H)1 and T(H)2 effector cells made? Curr Opin Immunol. 2009;21(2):153–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Rodriguez-Pinilla SM, Atienza L, Murillo C, Perez-Rodriguez A, Montes-Moreno S, Roncador G, et al. Peripheral T-cell lymphoma with follicular T-cell markers. Am J Surg Pathol. 2008;32(12):1787–99.

    Article  PubMed  Google Scholar 

  11. Zhan HQ, Li XQ, Zhu XZ, Lu HF, Zhou XY, Chen Y. Expression of follicular helper T cell markers in nodal peripheral T cell lymphomas: a tissue microarray analysis of 162 cases. J Clin Pathol. 2011;64(4):319–24.

    Article  PubMed  Google Scholar 

  12. Dupuis J, Boye K, Martin N, Copie-Bergman C, Plonquet A, Fabiani B, et al. Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL): a new diagnostic marker providing evidence that AITL derives from follicular helper T cells. Am J Surg Pathol. 2006;30(4):490–4.

    Article  PubMed  Google Scholar 

  13. de Leval L, Rickman DS, Thielen C, Reynies A, Huang YL, Delsol G, et al. 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. 2007;109(11):4952–63.

    Article  PubMed  Google Scholar 

  14. Piccaluga PP, Agostinelli C, Califano A, Carbone A, Fantoni L, Ferrari S, et al. Gene expression analysis of angioimmunoblastic lymphoma indicates derivation from T follicular helper cells and vascular endothelial growth factor deregulation. Cancer Res. 2007;67(22):10703–10.

    Article  CAS  PubMed  Google Scholar 

  15. Lemonnier F, Couronne L, Parrens M, Jais JP, Travert M, Lamant L, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120(7):1466–9.

    Article  CAS  PubMed  Google Scholar 

  16. Huang Y, Moreau A, Dupuis J, Streubel B, Petit B, Le Gouill S, et al. Peripheral T-cell lymphomas with a follicular growth pattern are derived from follicular helper T cells (TFH) and may show overlapping features with angioimmunoblastic T-cell lymphomas. Am J Surg Pathol. 2009;33(5):682–90.

    Article  PubMed  Google Scholar 

  17. Streubel B, Vinatzer U, Willheim M, Raderer M, Chott A. Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. Leukemia. 2006;20(2):313–8.

    Article  CAS  PubMed  Google Scholar 

  18. Pechloff K, Holch J, Ferch U, Schweneker M, Brunner K, Kremer M, et al. 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. 2010;207(5):1031–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Bach MP, Hug E, Werner M, Holch J, Sprissler C, Pechloff K, et al. Premature terminal differentiation protects from deregulated lymphocyte activation by ITK-Syk. J Immunol. 2014;192(3):1024–33.

    Article  CAS  PubMed  Google Scholar 

  20. Dierks C, Adrian F, Fisch P, Ma H, Maurer H, Herchenbach D, et al. The ITK-SYK fusion oncogene induces a T-cell lymphoproliferative disease in mice mimicking human disease. Cancer Res. 2010;70(15):6193–204.

    Article  CAS  PubMed  Google Scholar 

  21. de Leval L, Gisselbrecht C, Gaulard P. Advances in the understanding and management of angioimmunoblastic T-cell lymphoma. Br J Haematol. 2010;148(5):673–89.

    Article  PubMed  Google Scholar 

  22. Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais JP, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119(8):1901–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Abdel-Wahab O, Levine RL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood. 2013;121(18):3563–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson G, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059-74.

  25. Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46(2):166–70. RHOA mutations were identified in AITL. Ref 5 and 25 were concurrently published.

  26. Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(4):371–5.

  27. Bustelo XR, Sauzeau V, Berenjeno IM. GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo. Bioessays. 2007;29(4):356–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature. 2002;420(6916):629–35.

    Article  CAS  PubMed  Google Scholar 

  29. Muto H, Sakata-Yanagimoto M, Nagae G, Shiozawa Y, Miyake Y, Yoshida K, et al. Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice. Blood Cancer J. 2014;4:e264.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Morito N, Yoh K, Fujioka Y, Nakano T, Shimohata H, Hashimoto Y, et al. Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human. Cancer Res. 2006;66(2):812–9.

    Article  CAS  PubMed  Google Scholar 

  31. Yu D, Tan AH, Hu X, Athanasopoulos V, Simpson N, Silva DG, et al. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature. 2007;450(7167):299–303.

    Article  CAS  PubMed  Google Scholar 

  32. Ellyard JI, Chia T, Rodriguez-Pinilla SM, Martin JL, Hu X, Navarro-Gonzalez M, et al. Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice. Blood. 2012;120(4):812–21.

    Article  PubMed  Google Scholar 

  33. Auguste T, Travert M, Tarte K, Ame-Thomas P, Artchounin C, Martin-Garcia N, et al. ROQUIN/RC3H1 alterations are not found in angioimmunoblastic T-cell lymphoma. PLoS One. 2013;8(6):e64536.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Sato F, Ishida T, Ito A, Mori F, Masaki A, Takino H, et al. Angioimmunoblastic T-cell lymphoma mice model. Leuk Res. 2013;37(1):21–7.

    Article  CAS  PubMed  Google Scholar 

  35. Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmaki H, Andersson EI, et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med. 2012;366(20):1905–13. Activating STAT3 mutations were found in T-cell large granular lymphocytic leukemia (T-LGL).

  36. Jerez A, Clemente MJ, Makishima H, Koskela H, Leblanc F, Peng Ng K, et al. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood. 2012;120(15):3048–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Sakata-Yanagimoto M, Enami T, Yokoyama Y, Chiba S. Disease-specific mutations in mature lymphoid neoplasms: recent advances. Cancer Sci. 2014;105(6):623–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Kucuk C, Jiang B, Hu X, Zhang W, Chan JK, Xiao W, et al. Activating mutations of STAT5B and STAT3 in lymphomas derived from gammadelta-T or NK cells. Nat Commun. 2015;6:6025. Mutations in STAT3 and STAT5b were identified in various PTCLs.

  39. Ohgami RS, Ma L, Merker JD, Martinez B, Zehnder JL, Arber DA. STAT3 mutations are frequent in CD30+ T-cell lymphomas and T-cell large granular lymphocytic leukemia. Leukemia. 2013;27(11):2244–7.

    Article  CAS  PubMed  Google Scholar 

  40. Rajala HL, Eldfors S, Kuusanmaki H, van Adrichem AJ, Olson T, Lagstrom S, et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013;121(22):4541–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Nicolae A, Xi L, Pittaluga S, Abdullaev Z, Pack SD, Chen J, et al. Frequent STAT5B mutations in gammadelta hepatosplenic T-cell lymphomas. Leukemia. 2014;28(11):2244–8.

    Article  CAS  PubMed  Google Scholar 

  42. Kiel MJ, Velusamy T, Rolland D, Sahasrabuddhe AA, Chung F, Bailey NG, et al. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood. 2014;124(9):1460–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Iqbal J, Weisenburger DD, Chowdhury A, Tsai MY, Srivastava G, Greiner TC, et al. Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic gammadelta T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro. Leukemia. 2011;25(2):348–58.

    Article  CAS  PubMed  Google Scholar 

  44. Karube K, Tsuzuki S, Yoshida N, Arita K, Kato H, Katayama M, et al. Comprehensive gene expression profiles of NK cell neoplasms identify vorinostat as an effective drug candidate. Cancer Lett. 2013;333(1):47–55.

    Article  CAS  PubMed  Google Scholar 

  45. Huang Y, de Reynies A, de Leval L, Ghazi B, Martin-Garcia N, Travert M, et al. Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood. 2010;115(6):1226–37.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Koo GC, Tan SY, Tang T, Poon SL, Allen GE, Tan L, et al. Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov. 2012;2(7):591–7.

    Article  CAS  PubMed  Google Scholar 

  47. Bouchekioua A, Scourzic L, de Wever O, Zhang Y, Cervera P, Aline-Fardin A, et al. JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma. Leukemia. 2014;28(2):338–48.

    Article  CAS  PubMed  Google Scholar 

  48. Ng SB, Yan J, Huang G, Selvarajan V, Tay JL, Lin B, et al. Dysregulated microRNAs affect pathways and targets of biologic relevance in nasal-type natural killer/T-cell lymphoma. Blood. 2011;118(18):4919–29.

    Article  CAS  PubMed  Google Scholar 

  49. Suzuki R. Pathogenesis and treatment of extranodal natural killer/T-cell lymphoma. Semin Hematol. 2014;51(1):42–51.

    Article  CAS  PubMed  Google Scholar 

  50. Yamaguchi M, Kita K, Miwa H, Nishii K, Oka K, Ohno T, et al. Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells. Cancer. 1995;76(11):2351–6.

    Article  CAS  PubMed  Google Scholar 

  51. Takakuwa T, Dong Z, Nakatsuka S, Kojya S, Harabuchi Y, Yang WI, et al. Frequent mutations of Fas gene in nasal NK/T cell lymphoma. Oncogene. 2002;21(30):4702–5.

    Article  CAS  PubMed  Google Scholar 

  52. Jeon YK, Kim H, Park SO, Choi HY, Kim YA, Park SS, et al. Resistance to Fas-mediated apoptosis is restored by cycloheximide through the downregulation of cellular FLIPL in NK/T-cell lymphoma. Lab Invest. 2005;85(7):874–84.

    Article  CAS  PubMed  Google Scholar 

  53. Budd RC, Yeh WC, Tschopp J. cFLIP regulation of lymphocyte activation and development. Nat Rev Immunol. 2006;6(3):196–204.

    Article  CAS  PubMed  Google Scholar 

  54. Vockerodt M, Yap LF, Shannon-Lowe C, Curley H, Wei W, Vrzalikova K, et al. The Epstein-Barr virus and the pathogenesis of lymphoma. J Pathol. 2015;235(2):312–22.

    Article  PubMed  Google Scholar 

  55. George LC, Rowe M, Fox CP. Epstein-barr virus and the pathogenesis of T and NK lymphoma: a mystery unsolved. Curr Hematol Malig Rep. 2012;7(4):276–84.

    Article  PubMed  Google Scholar 

  56. Sun L, Zhao Y, Shi H, Ma C, Wei L. LMP-1 induces survivin expression to inhibit cell apoptosis through the NF-kappaB and PI3K/Akt signaling pathways in nasal NK/T-cell lymphoma. Oncol Rep. 2015;33(5):2253–60.

  57. Lin TC, Liu TY, Hsu SM, Lin CW. Epstein-Barr virus-encoded miR-BART20-5p inhibits T-bet translation with secondary suppression of p53 in invasive nasal NK/T-cell lymphoma. Am J Pathol. 2013;182(5):1865–75.

    Article  CAS  PubMed  Google Scholar 

  58. Kucuk C, Iqbal J, Hu X, Gaulard P, De Leval L, Srivastava G, et al. PRDM1 is a tumor suppressor gene in natural killer cell malignancies. Proc Natl Acad Sci U S A. 2011;108(50):20119–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Karube K, Nakagawa M, Tsuzuki S, Takeuchi I, Honma K, Nakashima Y, et al. Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses. Blood. 2011;118(12):3195–204.

    Article  CAS  PubMed  Google Scholar 

  60. Quintanilla-Martinez L, Kremer M, Keller G, Nathrath M, Gamboa-Dominguez A, Meneses A, et al. p53 Mutations in nasal natural killer/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease. Am J Pathol. 2001;159(6):2095–105.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Lee JH, Cho SJ, Zhang X, Zheng Z, Lee ES, Kim A, et al. nm23-H1 protein expression and gene mutation in 150 patients with non-Hodgkin’s lymphomas. J Korean Med Sci. 2006;21(4):645–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Kimura H, Karube K, Ito Y, Hirano K, Suzuki M, Iwata S, et al. Rare occurrence of JAK3 mutations in natural killer cell neoplasms in Japan. Leuk Lymphoma. 2014;55(4):962–3.

  63. Ambrogio C, Martinengo C, Voena C, Tondat F, Riera L, di Celle PF, et al. NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells. Cancer Res. 2009;69(22):8611–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008;8(1):11–23.

    Article  CAS  PubMed  Google Scholar 

  65. Falini B, Nicoletti I, Bolli N, Martelli MP, Liso A, Gorello P, et al. Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias. Haematologica. 2007;92(4):519–32.

    Article  CAS  PubMed  Google Scholar 

  66. Mano H. ALKoma: a cancer subtype with a shared target. Cancer Discov. 2012;2(6):495–502.

    Article  CAS  PubMed  Google Scholar 

  67. Feldman AL, Dogan A, Smith DI, Law ME, Ansell SM, Johnson SH, et al. Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. Blood. 2011;117(3):915–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014;124(9):1473–80. ALK-negative ALCL was subclassified by recurrent translocations.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Vasmatzis G, Johnson SH, Knudson RA, Ketterling RP, Braggio E, Fonseca R, et al. Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas. Blood. 2012;120(11):2280–9.

    Article  CAS  PubMed  Google Scholar 

  70. Piva R, Agnelli L, Pellegrino E, Todoerti K, Grosso V, Tamagno I, et al. Gene expression profiling uncovers molecular classifiers for the recognition of anaplastic large-cell lymphoma within peripheral T-cell neoplasms. J Clin Oncol. 2010;28(9):1583–90.

    Article  CAS  PubMed  Google Scholar 

  71. Lim MS, Carlson ML, Crockett DK, Fillmore GC, Abbott DR, Elenitoba-Johnson OF, et al. The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways. Blood. 2009;114(8):1585–95.

    Article  CAS  PubMed  Google Scholar 

  72. Chiarle R, Simmons WJ, Cai H, Dhall G, Zamo A, Raz R, et al. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nat Med. 2005;11(6):623–9.

    Article  CAS  PubMed  Google Scholar 

  73. Marzec M, Kasprzycka M, Liu X, El-Salem M, Halasa K, Raghunath PN, et al. Oncogenic tyrosine kinase NPM/ALK induces activation of the rapamycin-sensitive mTOR signaling pathway. Oncogene. 2007;26(38):5606–14.

    Article  CAS  PubMed  Google Scholar 

  74. Laimer D, Dolznig H, Kollmann K, Vesely PW, Schlederer M, Merkel O, et al. PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nat Med. 2012;18(11):1699–704.

    Article  CAS  PubMed  Google Scholar 

  75. Lamant L, de Reynies A, Duplantier MM, Rickman DS, Sabourdy F, Giuriato S, et al. Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes. Blood. 2007;109(5):2156–64.

    Article  CAS  PubMed  Google Scholar 

  76. Merkel O, Hamacher F, Laimer D, Sifft E, Trajanoski Z, Scheideler M, et al. Identification of differential and functionally active miRNAs in both anaplastic lymphoma kinase (ALK) + and ALK- anaplastic large-cell lymphoma. Proc Natl Acad Sci U S A. 2010;107(37):16228–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Mehrotra M, Medeiros LJ, Luthra R, Sargent RL, Yao H, Barkoh BA, et al. Identification of putative pathogenic microRNA and its downstream targets in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Hum Pathol. 2014;45(10):1995–2005.

    Article  CAS  PubMed  Google Scholar 

  78. Merkel O, Hamacher F, Griessl R, Grabner L, Schiefer AI, Prutsch N, et al. Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation. J Pathol. 2015;236(4):445–56.

  79. Matsuyama H, Suzuki HI, Nishimori H, Noguchi M, Yao T, Komatsu N, et al. miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood. 2011;118(26):6881–92.

    Article  CAS  PubMed  Google Scholar 

  80. Dejean E, Renalier MH, Foisseau M, Agirre X, Joseph N, de Paiva GR, et al. Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas. Leukemia. 2011;25(12):1882–90.

    Article  CAS  PubMed  Google Scholar 

  81. Desjobert C, Renalier MH, Bergalet J, Dejean E, Joseph N, Kruczynski A, et al. MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression. Blood. 2011;117(24):6627–37.

    Article  CAS  PubMed  Google Scholar 

  82. Jager R, Hahne J, Jacob A, Egert A, Schenkel J, Wernert N, et al. Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas. Anticancer Res. 2005;25(5):3191–6.

    PubMed  Google Scholar 

  83. Chiarle R, Gong JZ, Guasparri I, Pesci A, Cai J, Liu J, et al. NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors. Blood. 2003;101(5):1919–27.

    Article  CAS  PubMed  Google Scholar 

  84. Turner SD, Tooze R, Maclennan K, Alexander DR. Vav-promoter regulated oncogenic fusion protein NPM-ALK in transgenic mice causes B-cell lymphomas with hyperactive Jun kinase. Oncogene. 2003;22(49):7750–61.

    Article  CAS  PubMed  Google Scholar 

  85. Turner SD, Merz H, Yeung D, Alexander DR. CD2 promoter regulated nucleophosmin-anaplastic lymphoma kinase in transgenic mice causes B lymphoid malignancy. Anticancer Res. 2006;26(5A):3275–9.

    CAS  PubMed  Google Scholar 

  86. Miething C, Grundler R, Fend F, Hoepfl J, Mugler C, von Schilling C, et al. The oncogenic fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) induces two distinct malignant phenotypes in a murine retroviral transplantation model. Oncogene. 2003;22(30):4642–7.

    Article  CAS  PubMed  Google Scholar 

  87. Pfeifer W, Levi E, Petrogiannis-Haliotis T, Lehmann L, Wang Z, Kadin ME. A murine xenograft model for human CD30+ anaplastic large cell lymphoma. Successful growth inhibition with an anti-CD30 antibody (HeFi-1). Am J Pathol. 1999;155(4):1353–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Ko M, An J, Pastor WA, Koralov SB, Rajewsky K, Rao A. TET proteins and 5-methylcytosine oxidation in hematological cancers. Immunol Rev. 2015;263(1):6–21.

    Article  CAS  PubMed  Google Scholar 

  89. Yang L, Rau R, Goodell MA. DNMT3A in haematological malignancies. Nat Rev Cancer. 2015;15(3):152–65.

    Article  CAS  PubMed  Google Scholar 

  90. Jan M, Snyder TM, Corces-Zimmerman MR, Vyas P, Weissman IL, Quake SR, et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci Transl Med. 2012;4(149):149ra18.

    Google Scholar 

  91. Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506(7488):328–33.

    Article  CAS  PubMed  Google Scholar 

  92. Busque L, Patel JP, Figueroa ME, Vasanthakumar A, Provost S, Hamilou Z, et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet. 2012;44(11):1179–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488–98.

  94. Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477–87.

  95. Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014;20(12):1472–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We appreciate Prof. Philippe Gaulard for his helpful discussions. This work is supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI 25461407) to Mamiko Sakata-Yanagimoto.

Compliance with Ethics Guidelines

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Conflict of Interest

Mamiko Sakata-Yanagimoto and Shigeru Chiba have a patent pending for detection technology for T cell lymphoma (PCT/JP2014/62112).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Department of Hematology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Mamiko Sakata-Yanagimoto & Shigeru Chiba

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  1. Mamiko Sakata-Yanagimoto
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  2. Shigeru Chiba
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Correspondence to Mamiko Sakata-Yanagimoto.

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This article is part of the Topical Collection on T Cell and Other Lymphoproliferative Malignancies

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Sakata-Yanagimoto, M., Chiba, S. Molecular Pathogenesis of Peripheral T Cell Lymphoma. Curr Hematol Malig Rep 10, 429–437 (2015). https://doi.org/10.1007/s11899-015-0289-7

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  • DOI: https://doi.org/10.1007/s11899-015-0289-7

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