Skip to main content
SpringerLink
Log in

Molecular Profiling and Prognosis in T-Cell Lymphomas

  • Chapter
  • First Online:
Book cover T-Cell Lymphomas

Part of the book series: Contemporary Hematology ((CH))

  • 1249 Accesses

Abstract

Gene expression profile (GEP) studies have provided important insights into the histogenesis and molecular pathogenesis of aggressive T-cell lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) corresponds to T-follicular helper (TFH) lymphocytes and presents consistent deregulation of genes involved in angiogenesis. PTCLs/NOS include at least three different subset characterized by specific cellular derivation (T-central memory, T-cytotoxic and TFH), and possibly different outcome. Besides that, notably, all PTCLs/NOS present with constant deregulation of certain molecules, including the PDGFRA, which represents a suitable therapeutic target in this setting. Finally, both ALK+ and ALK− ALCLs have been shown to be distinct from the other PTCLs, possibly constituting separate entities. As far as prognostication of PTCLs is concerned, the IPI (based on age, performance status, LDH, stage, and extranodal involvement) appears to be efficient as prognostic factor in PTCLs, at least in part and especially for certain PTCL subtypes. However, it is not definitely satisfactory for the two commonest PTCLs, the not otherwise specified (NOS) and the angioimmunoblastic types (AITL). Thus, novel scores, possibly based on the biological features of the tumors have been explored. More recently, GEP has been used for the identification of novel molecular prognostic factors. In particular, inactivation of the NFκB pathway, high expression of proliferation-associated genes, and cytotoxic molecular phenotype seemed to be associated to a worse outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Harris NL, Jaffe ES, Stein H, et al. A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84(5):1361–92.

    PubMed  CAS  Google Scholar 

  2. The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood. 1997;89(11):3909–18.

    Google Scholar 

  3. WHO. Classification of tumors of hematopoietic and lymphoid tissues. IVth ed. Lyon: IARC; 2008.

    Google Scholar 

  4. Pileri S, Ralfkiaer E, Weisenburger D, et al. Peripheral T-cell lymphoma, not otherwise specified. In: Swerdlow S, Campo E, Harris NL, et al., editors. WHO Classification of tumors of hematopoietic and lymphoid tissues. IVth ed. Lyon: IARC; 2008. p. 429.

    Google Scholar 

  5. Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–30.

    PubMed  Google Scholar 

  6. Savage KJ, Harris NL, Vose JM, et al. ALK-anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK  +  ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. 2008;111(12):5496–504.

    PubMed  CAS  Google Scholar 

  7. Evens AM, Gartenhaus RB. Treatment of T-cell non-Hodgkin’s lymphoma. Curr Treat Options Oncol. 2004;5(4):289–303.

    PubMed  Google Scholar 

  8. Lopez-Guillermo A, Cid J, Salar A, et al. Peripheral T-cell lymphomas: initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. Classification. Ann Oncol. 1998;9(8):849–55.

    PubMed  CAS  Google Scholar 

  9. Gisselbrecht C, Gaulard P, Lepage E, et al. Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Groupe d’Etudes des Lymphomes de l’Adulte (GELA). Blood. 1998;92(1):76–82.

    PubMed  CAS  Google Scholar 

  10. Effect of age on the characteristics and clinical behavior of non-Hodgkin’s lymphoma patients. The Non-Hodgkin’s Lymphoma Classification Project. Ann Oncol. 1997;8(10):973–8.

    Google Scholar 

  11. Went P, Agostinelli C, Gallamini A, et al. Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol. 2006;24(16):2472–9.

    PubMed  CAS  Google Scholar 

  12. Rudiger T, Weisenburger DD, Anderson JR, et al. Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin’s Lymphoma Classification Project. Ann Oncol. 2002;13(1):140–9.

    PubMed  CAS  Google Scholar 

  13. Zettl A, Rudiger T, Konrad MA, et al. Genomic profiling of peripheral T-cell lymphoma, unspecified, and anaplastic large T-cell lymphoma delineates novel recurrent chromosomal alterations. Am J Pathol. 2004;164(5):1837–48.

    PubMed  CAS  Google Scholar 

  14. Oshiro A, Tagawa H, Ohshima K, et al. Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma. Blood. 2006;107(11):4500–7.

    PubMed  CAS  Google Scholar 

  15. Hartmann S, Gesk S, Scholtysik R, et al. High resolution SNP array genomic profiling of peripheral T cell lymphomas, not otherwise specified, identifies a subgroup with chromosomal aberrations affecting the REL locus. Br J Haematol. 2010;148(3):402–12.

    PubMed  Google Scholar 

  16. Ascani S, Zinzani PL, Gherlinzoni F, et al. Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. Classification. Ann Oncol. 1997;8(6):583–92.

    PubMed  CAS  Google Scholar 

  17. Piccaluga PP, Agostinelli C, Califano A, et al. Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets. J Clin Invest. 2007;117(3):823–34.

    PubMed  CAS  Google Scholar 

  18. Piva R, Agnelli L, Pellegrino E, 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.

    PubMed  CAS  Google Scholar 

  19. Tracey L, Villuendas R, Dotor AM, et al. Mycosis fungoides shows concurrent deregulation of multiple genes involved in the TNF signaling pathway: an expression profile study. Blood. 2003;102(3):1042–50.

    PubMed  CAS  Google Scholar 

  20. Martinez-Delgado B, Melendez B, Cuadros M, et al. Expression profiling of T-cell lymphomas differentiates peripheral and lymphoblastic lymphomas and defines survival related genes. Clin Cancer Res. 2004;10(15):4971–82.

    PubMed  CAS  Google Scholar 

  21. Martinez-Delgado B, Cuadros M, Honrado E, et al. Differential expression of NF-kappaB pathway genes among peripheral T-cell lymphomas. Leukemia. 2005;19(12):2254–63.

    PubMed  CAS  Google Scholar 

  22. Piccaluga PP, Agostinelli C, Zinzani PL, Baccarani M, Dalla Favera R, Pileri SA. Expression of platelet-derived growth factor receptor alpha in peripheral T-cell lymphoma not otherwise specified. Lancet Oncol. 2005;6(6):440.

    PubMed  Google Scholar 

  23. Ballester B, Ramuz O, Gisselbrecht C, et al. Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas. Oncogene. 2006;25(10):1560–70.

    PubMed  CAS  Google Scholar 

  24. Mahadevan D, Spier C, Della Croce K, et al. Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures. Mol Cancer Ther. 2005;4(12):1867–79.

    PubMed  CAS  Google Scholar 

  25. Lamant L, de Reynies A, Duplantier MM, 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.

    PubMed  CAS  Google Scholar 

  26. de Leval L, Rickman DS, Thielen C, 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.

    PubMed  Google Scholar 

  27. Cuadros M, Dave SS, Jaffe ES, et al. Identification of a proliferation signature related to survival in nodal peripheral T-cell lymphomas. J Clin Oncol. 2007;25(22):3321–9.

    PubMed  Google Scholar 

  28. Piccaluga PP, Agostinelli C, Califano A, 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.

    PubMed  CAS  Google Scholar 

  29. Miyazaki K, Yamaguchi M, Imai H, et al. Gene expression profiling of peripheral T-cell lymphoma including gammadelta T-cell lymphoma. Blood. 2009;113(5):1071–4.

    PubMed  CAS  Google Scholar 

  30. Pise-Masison CA, Radonovich M, Dohoney K, et al. Gene expression profiling of ATL patients: compilation of disease-related genes and evidence for TCF4 involvement in BIRC5 gene expression and cell viability. Blood. 2009;113(17):4016–26.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  32. Iqbal J, Weisenburger DD, Greiner TC, 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.

    PubMed  CAS  Google Scholar 

  33. Dave SS, Wright G, Tan B, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004;351(21):2159–69.

    PubMed  CAS  Google Scholar 

  34. Steidl C, Lee T, Shah SP, et al. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362(10):875–85.

    PubMed  CAS  Google Scholar 

  35. Watson A, Mazumder A, Stewart M, Balasubramanian S. Technology for microarray analysis of gene expression. Curr Opin Biotechnol. 1998;9(6):609–14.

    PubMed  CAS  Google Scholar 

  36. Dupuis J, Boye K, Martin N, 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.

    PubMed  Google Scholar 

  37. Grogg KL, Attygale AD, Macon WR, Remstein ED, Kurtin PJ, Dogan A. Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified. Mod Pathol. 2006;19(8):1101–7.

    PubMed  CAS  Google Scholar 

  38. Roncador G, Garcia Verdes-Montenegro JF, Tedoldi S, et al. Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma. Haematologica. 2007;92(8):1059–66.

    PubMed  CAS  Google Scholar 

  39. Marafioti T, Paterson JC, Ballabio E, et al. The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation. Haematologica. 2010;95(3):432–9.

    PubMed  CAS  Google Scholar 

  40. Laurent C, Fazilleau N, Brousset P. A novel subset of T-helper cells: follicular T-helper cells and their markers. Haematologica. 2010;95(3):356–8.

    PubMed  CAS  Google Scholar 

  41. Rudiger T, Geissinger E, Muller-Hermelink HK. ‘Normal counterparts’ of nodal peripheral T-cell lymphoma. Hematol Oncol. 2006;24(4):175–80.

    PubMed  Google Scholar 

  42. Huang Y, Moreau A, Dupuis J, 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.

    PubMed  Google Scholar 

  43. Tapper J, Kettunen E, El-Rifai W, Seppala M, Andersson LC, Knuutila S. Changes in gene expression during progression of ovarian carcinoma. Cancer Genet Cytogenet. 2001;128(1):1–6.

    PubMed  CAS  Google Scholar 

  44. Sado Y, Kagawa M, Naito I, et al. Organization and expression of basement membrane collagen IV genes and their roles in human disorders. J Biochem (Tokyo). 1998;123(5):767–76.

    CAS  Google Scholar 

  45. van den Boom J, Wolter M, Kuick R, et al. Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am J Pathol. 2003;163(3):1033–43.

    PubMed  Google Scholar 

  46. Jin S, Tong T, Fan W, et al. GADD45-induced cell cycle G2-M arrest associates with altered subcellular distribution of cyclin B1 and is independent of p38 kinase activity. Oncogene. 2002;21(57):8696–704.

    PubMed  CAS  Google Scholar 

  47. Papa S, Zazzeroni F, Bubici C, et al. Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2. Nat Cell Biol. 2004;6(2):146–53.

    PubMed  CAS  Google Scholar 

  48. Chen F, Lu Y, Zhang Z, et al. Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite. J Biol Chem. 2001;276(14):11414–9.

    PubMed  CAS  Google Scholar 

  49. Hirose T, Sowa Y, Takahashi S, et al. p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate regulation by transcription factors Oct-1 and NF-Y. Oncogene. 2003;22(49):7762–73.

    PubMed  CAS  Google Scholar 

  50. Tan KO, Tan KM, Chan SL, et al. MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J Biol Chem. 2001;276(4):2802–7.

    PubMed  CAS  Google Scholar 

  51. Nagashima M, Shiseki M, Pedeux RM, et al. A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control, and apoptosis. Oncogene. 2003;22(3):343–50.

    PubMed  CAS  Google Scholar 

  52. Gunduz M, Ouchida M, Fukushima K, et al. Allelic loss and reduced expression of the ING3, a candidate tumor suppressor gene at 7q31, in human head and neck cancers. Oncogene. 2002;21(28):4462–70.

    PubMed  CAS  Google Scholar 

  53. Lee MS, Hanspers K, Barker CS, Korn AP, McCune JM. Gene expression profiles during human CD4+ T cell differentiation. Int Immunol. 2004;16(8):1109–24.

    PubMed  CAS  Google Scholar 

  54. Chtanova T, Newton R, Liu SM, et al. Identification of T cell-restricted genes, and signatures for different T cell responses, using a comprehensive collection of microarray datasets. J Immunol. 2005;175(12):7837–47.

    PubMed  CAS  Google Scholar 

  55. Chtanova T, Tangye SG, Newton R, et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol. 2004;173(1):68–78.

    PubMed  CAS  Google Scholar 

  56. Hosack DA, Dennis Jr G, Sherman BT, Lane HC, Lempicki RA. Identifying biological themes within lists of genes with EASE. Genome Biol. 2003;4(10):R70.

    PubMed  Google Scholar 

  57. Han JS, Macarak E, Rosenbloom J, Chung KC, Chaqour B. Regulation of Cyr61/CCN1 gene expression through RhoA GTPase and p38MAPK signaling pathways. Eur J Biochem. 2003;270(16):3408–21.

    PubMed  CAS  Google Scholar 

  58. Leu SJ, Liu Y, Chen N, Chen CC, Lam SC, Lau LF. Identification of a novel integrin alpha 6 beta 1 binding site in the angiogenic inducer CCN1 (CYR61). J Biol Chem. 2003;278(36):33801–8.

    PubMed  CAS  Google Scholar 

  59. Schober JM, Lau LF, Ugarova TP, Lam SC. Identification of a novel integrin alphaMbeta2 binding site in CCN1 (CYR61), a matricellular protein expressed in healing wounds and atherosclerotic lesions. J Biol Chem. 2003;278(28):25808–15.

    PubMed  CAS  Google Scholar 

  60. Tsai MS, Bogart DF, Castaneda JM, Li P, Lupu R. Cyr61 promotes breast tumorigenesis and cancer progression. Oncogene. 2002;21(53):8178–85.

    PubMed  CAS  Google Scholar 

  61. Tsai MS, Hornby AE, Lakins J, Lupu R. Expression and function of CYR61, an angiogenic factor, in breast cancer cell lines and tumor biopsies. Cancer Res. 2000;60(20):5603–7.

    PubMed  CAS  Google Scholar 

  62. Lin MT, Chang CC, Chen ST, et al. Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation. J Biol Chem. 2004;279(23):24015–23.

    PubMed  CAS  Google Scholar 

  63. Kassem H, Sangar V, Cowan R, Clarke N, Margison GP. A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer. Int J Cancer. 2002;101(5):454–60.

    PubMed  CAS  Google Scholar 

  64. Xu J, Capezzone M, Xu X, Hershman JM. Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1{beta} in human papillary thyroid cancer cells. Mol Endocrinol. 2005;19(2):527–39.

    PubMed  CAS  Google Scholar 

  65. Piccaluga P, Agostinelli C, Righi S, et al. Expression of classical NF-kappa B pathway molecules in peripheral t-cell lymphoma not otherwise specified. In: 10th International Conference on Malignant Lymphoma; 2008 June, 4–6; 2008; Lugano, CH; 2008. p. #231.

    Google Scholar 

  66. Briones J, Moga E, Espinosa I, et al. Bcl-10 protein highly correlates with the expression of phosphorylated p65 NF-kappaB in peripheral T-cell lymphomas and is associated with clinical outcome. Histopathology. 2009;54(4):478–85.

    PubMed  Google Scholar 

  67. Piccaluga P, Rossi M, De Falco G, et al. PDGFRA activity deregulation in PTCL/NOS is a consequence of miRNA deregulation and autocrine loop sustainment. In: American Association for Cancer Research Annual Meeting; 2009 April 18–22; Denver Philadelphia (PA): AACR; 2009.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  69. Chiarle R, Martinengo C, Mastini C, et al. The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination. Nat Med. 2008;14(6):676–80.

    PubMed  CAS  Google Scholar 

  70. Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 2007;109(1):31–9.

    PubMed  CAS  Google Scholar 

  71. Sanchez-Gonzalez B, Yang H, Bueso-Ramos C, et al. Antileukemia activity of the combination of an anthracycline with a histone deacetylase inhibitor. Blood. 2006;108(4):1174–82.

    PubMed  CAS  Google Scholar 

  72. Strupp C, Aivado M, Germing U, Gattermann N, Haas R. Angioimmunoblastic lymphadenopathy (AILD) may respond to thalidomide treatment: two case reports. Leuk Lymphoma. 2002;43(1):133–7.

    PubMed  CAS  Google Scholar 

  73. Bruns I, Fox F, Reinecke P, et al. Complete remission in a patient with relapsed angioimmunoblastic T-cell lymphoma following treatment with bevacizumab. Leukemia. 2005;19(11):1993–5.

    PubMed  CAS  Google Scholar 

  74. Dogan A, Ngu LS, Ng SH, Cervi PL. Pathology and clinical features of angioimmunoblastic T-cell lymphoma after successful treatment with thalidomide. Leukemia. 2005;19(5):873–5.

    PubMed  CAS  Google Scholar 

  75. Ramasamy K, Lim Z, Pagliuca A, Salisbury JR, Mufti GJ, Devereux S. Successful treatment of refractory angioimmunoblastic T-cell lymphoma with thalidomide and dexamethasone. Haematologica 2006;91(8 Suppl): ECR44.

    Google Scholar 

  76. Aguiar Bujanda D. Complete response of relapsed angioimmunoblastic T-cell lymphoma following therapy with bevacizumab. Ann Oncol. 2008;19(2):396–7.

    PubMed  CAS  Google Scholar 

  77. Gottardi M, Danesin C, Canal F, et al. Complete remission induced by thalidomide in a case of angioimmunoblastic T-cell lymphoma refractory to autologous stem cell transplantation. Leuk Lymphoma. 2008;49(9):1836–8.

    PubMed  Google Scholar 

  78. Kim YH, Duvic M, Obitz E, et al. Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma. Blood. 2007;109(11):4655–62.

    PubMed  CAS  Google Scholar 

  79. Enblad G, Hagberg H, Erlanson M, et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood. 2004;103(8):2920–4.

    PubMed  CAS  Google Scholar 

  80. Gallamini A, Zaja F, Patti C, et al. Alemtuzumab (Campath-1 H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter trial. Blood. 2007;110(7):2316–23.

    PubMed  CAS  Google Scholar 

  81. Piccaluga PP, Agostinelli C, Righi S, Zinzani PL, Pileri SA. Expression of CD52 in peripheral T-cell lymphoma. Haematologica. 2007;92(4):566–7.

    PubMed  Google Scholar 

  82. Rodig SJ, Abramson JS, Pinkus GS, et al. Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1 H). Clin Cancer Res. 2006;12(23):7174–9.

    PubMed  CAS  Google Scholar 

  83. Chang ST, Lu CL, Chuang SS. CD52 expression in non-mycotic T- and NK/T-cell lymphomas. Leuk Lymphoma. 2007;48(1):117–21.

    PubMed  Google Scholar 

  84. A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329(14):987–94.

    Google Scholar 

  85. Falini B, Pileri S, Zinzani PL, et al. ALK  +  lymphoma: clinico-pathological findings and outcome. Blood. 1999;93(8):2697–706.

    PubMed  CAS  Google Scholar 

  86. Suzumiya J, Ohshima K, Tamura K, et al. The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-Cell Lymphoma Project. Ann Oncol. 2009;20(4):715–21.

    PubMed  CAS  Google Scholar 

  87. Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. Blood. 2004;103(7):2474–9.

    PubMed  CAS  Google Scholar 

  88. Cheng AL, Su IJ, Chen YC, Uen WC, Wang CH. Characteristic clinicopathologic features of Epstein-Barr virus-associated peripheral T-cell lymphoma. Cancer. 1993;72(3):909–16.

    PubMed  CAS  Google Scholar 

  89. Kluin PM, Feller A, Gaulard P, et al. Peripheral T/NK-cell lymphoma: a report of the IXth Workshop of the European Association for Haematopathology. Histopathology. 2001;38(3):250–70.

    PubMed  CAS  Google Scholar 

  90. Dupuis J, Emile JF, Mounier N, et al. Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d’Etude des Lymphomes de l’Adulte (GELA) study. Blood. 2006;108(13):4163–9.

    PubMed  CAS  Google Scholar 

  91. Bekkenk MW, Vermeer MH, Jansen PM, et al. Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients. Blood. 2003;102(6):2213–9.

    PubMed  CAS  Google Scholar 

  92. Kojima H, Hasegawa Y, Suzukawa K, et al. Clinicopathological features and prognostic factors of Japanese patients with “peripheral T-cell lymphoma, unspecified” diagnosed according to the WHO classification. Leuk Res. 2004;28(12):1287–92.

    PubMed  Google Scholar 

  93. Caulet-Maugendre S, Patey M, Granier E, Joundi A, Gentile A, Caulet T. Quantitative analysis of cellular proliferative activity in 35 T-cell non-Hodgkin’s lymphomas. Use of proliferating cell nuclear antigen and Ki-67 (MIB-1) antibodies and nucleolar organizer regions. Anal Quant Cytol Histol. 1996;18(5):337–44.

    PubMed  CAS  Google Scholar 

  94. Miller TP, Grogan TM, Dahlberg S, et al. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin’s lymphomas: a prospective Southwest Oncology Group trial. Blood. 1994;83(6):1460–6.

    PubMed  CAS  Google Scholar 

  95. Mochen C, Giardini R, Costa A, Silvestrini R. MIB-1 and S-phase cell fraction predict survival in non-Hodgkin’s lymphomas. Cell Prolif. 1997;30(1):37–47.

    PubMed  CAS  Google Scholar 

  96. Montalban C, Obeso G, Gallego A, Castrillo JM, Bellas C, Rivas C. Peripheral T-cell lymphoma: a clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification. Histopathology. 1993;22(4):303–10.

    PubMed  CAS  Google Scholar 

  97. Sheval EV, Churakova JV, Dudnik OA, Vorobjev IA. Examination of the proliferative activity of tumor cells in human lymphoid neoplasms using a morphometric approach. Cancer. 2004;102(3):174–85.

    PubMed  Google Scholar 

  98. Tiemann M, Schrader C, Klapper W, et al. Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. Br J Haematol. 2005;131(1):29–38.

    PubMed  Google Scholar 

  99. Gazzola A, Bertuzzi C, Agostinelli C, Righi S, Pileri SA, Piccaluga PP. Physiological PTEN expression in peripheral T-cell lymphoma not otherwise specified. Haematologica. 2009;94(7):1036–7.

    PubMed  Google Scholar 

  100. Rodriguez-Antona C, Leskela S, Zajac M, et al. Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas. Blood. 2007;110(9):3345–51.

    PubMed  CAS  Google Scholar 

  101. Agostinelli C, Piccaluga PP, Went P, et al. Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies. J Clin Pathol. 2008;61(11):1160–7.

    PubMed  CAS  Google Scholar 

  102. Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362(15):1417–29.

    PubMed  CAS  Google Scholar 

  103. Quintanilla-Martinez L, Franklin JL, Guerrero I, et al. Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression. Hum Pathol. 1999;30(7):849–55.

    PubMed  CAS  Google Scholar 

  104. Oshimi K, Kawa K, Nakamura S, et al. NK-cell neoplasms in Japan. Hematology. 2005;10(3):237–45 (Amsterdam, Netherlands).

    PubMed  Google Scholar 

  105. Lee J, Suh C, Park YH, et al. Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol. 2006;24(4):612–8.

    PubMed  Google Scholar 

  106. Barrionuevo C, Zaharia M, Martinez MT, et al. Extranodal NK/T-cell lymphoma, nasal type: study of clinicopathologic and prognosis factors in a series of 78 cases from Peru. Appl Immunohistochem Mol Morphol. 2007;15(1):38–44.

    PubMed  Google Scholar 

  107. Chan J, Quintanilla-Martinez L, Ferry J, Peh S-C. Extranodal NK/T-cell lymphoma, nasal-type. In: Swerdlow S, Campo E, Harris NL, et al., editors. WHO Classification of tumors of hematopoietic and lymphoid tissues. IVth ed. Lyon: IARC; 2008. p. 285.

    Google Scholar 

  108. Au WY, Weisenburger DD, Intragumtornchai T, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood. 2009;113(17):3931–7.

    PubMed  CAS  Google Scholar 

  109. Kwong YL, Chan AC, Liang R, et al. CD56+ NK lymphomas: clinicopathological features and prognosis. Br J Haematol. 1997;97(4):821–9.

    PubMed  CAS  Google Scholar 

  110. Chan JK. Natural killer cell neoplasms. Anat Pathol. 1998;3:77–145.

    PubMed  CAS  Google Scholar 

  111. Cheung MM, Chan JK, Lau WH, Ngan RK, Foo WW. Early stage nasal NK/T-cell lymphoma: clinical outcome, prognostic factors, and the effect of treatment modality. Int J Radiat Oncol Biol Phys. 2002;54(1):182–90.

    PubMed  Google Scholar 

  112. Kuo TT, Shih LY, Tsang NM. Nasal NK/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities. Int J Surg Pathol. 2004;12(4):375–87.

    PubMed  CAS  Google Scholar 

  113. Au WY, Pang A, Choy C, Chim CS, Kwong YL. Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients. Blood. 2004;104(1):243–9.

    PubMed  CAS  Google Scholar 

  114. Ng SB, Lai KW, Murugaya S, et al. Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore. Mod Pathol. 2004;17(9):1097–107.

    PubMed  Google Scholar 

  115. Chim CS, Ma SY, Au WY, et al. Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the International Prognostic Index. Blood. 2004;103(1):216–21.

    PubMed  CAS  Google Scholar 

  116. Huang WT, Chang KC, Huang GC, et al. Bone marrow that is positive for Epstein-Barr virus encoded RNA-1 by in situ hybridization is related with a poor prognosis in patients with extranodal natural killer/T-cell lymphoma, nasal type. Haematologica. 2005;90(8):1063–9.

    PubMed  CAS  Google Scholar 

  117. Lee J, Suh C, Huh J, et al. Effect of positive bone marrow EBV in situ hybridization in staging and survival of localized extranodal natural killer/T-cell lymphoma, nasal-type. Clin Cancer Res. 2007;13(11):3250–4.

    PubMed  CAS  Google Scholar 

  118. Suzuki R, Suzumiya J, Yamaguchi M, et al. Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. Ann Oncol. 2010;21(5):1032–40.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Haematopathology Section, Department of Hematology and Oncological Sciences “L. and A. Seràgnoli”, S. Orsola-Malpighi Hospital, Pavillon 8, Via Massarenti 9, 40138, Bologna, Italy

    Pier Paolo Piccaluga & Stefano Aldo Pileri

Authors
  1. Pier Paolo Piccaluga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefano Aldo Pileri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefano Aldo Pileri .

Editor information

Editors and Affiliations

  1. Yale University School of Medicine, Dept. of Medical Oncology/Hematology, Cedar Street 333, New Haven, 06520, Connecticut, USA

    Francine Foss

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Piccaluga, P.P., Pileri, S.A. (2013). Molecular Profiling and Prognosis in T-Cell Lymphomas. In: Foss, F. (eds) T-Cell Lymphomas. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-170-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-170-7_3

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-169-1

  • Online ISBN: 978-1-62703-170-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation