Advertisement

Molecular Genetics of Mature T/NK Neoplasms

  • John P. Greer
  • Utpal P. Davé
  • Nishitha Reddy
  • Christine M. Lovly
  • Claudio A. Mosse
Chapter
Part of the Molecular Pathology Library book series (MPLB, volume 4)

Abstract

The mature (postthymocyte; peripheral) T/natural killer (NK) lymphomas/leukemias represent 5–15% of all non-Hodgkin lymphoma (NHL) and vary according to geography. Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS), is the most common type worldwide. There are more nodal presentations in Europe and North America, where the second most common types in each region are angioimmunoblastic T cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL), respectively. There is more extranodal disease in Asia, due to Epstein–Barr virus related NK/T lymphoma and human T cell leukemia virus (HTLV)-1 associated adult T cell leukemia/lymphoma (ATLL). With the exceptions of the indolent mycosis fungoides (MF) and the chemo-sensitive anaplastic lymphoma kinase (ALK)-positive ALCL, the prognosis in most peripheral T/NK neoplasms is poor, with a 5-year survival less than 30%. (Table 25.1)

Keywords

Anaplastic Lymphoma Kinase Anaplastic Large Cell Lymphoma Mycosis Fungoides Anaplastic Lymphoma Kinase Fusion Blastic Plasmacytoid Dendritic Cell Neoplasm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Armitage J, Vose J, Weisenburger D. et al. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–4130.PubMedGoogle Scholar
  2. 2.
    Greer JP. Therapy of peripheral T/NK neoplasms. Hematology Am Soc Hematol Educ Program. 2006;331–337.Google Scholar
  3. 3.
    Lukes RJ, Collins RD. Immunologic characterization of human malignant lymphomas. Cancer. 1974;34(4 Suppl):1488–1503.PubMedGoogle Scholar
  4. 4.
    Swerdlow SH, Campo E, Harris NL, et al., eds. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008.Google Scholar
  5. 5.
    Evens AM, Gartenhaus RB. Molecular etiology of mature T-cell non-Hodgkin’s lymphomas. Front Biosci. 2003;8:d156–d175.PubMedGoogle Scholar
  6. 6.
    Nelson M, Horsman DE, Weisenburger DD, et al. Cytogenetic abnormalities and clinical correlations in peripheral T-cell lymphoma. Br J Haematol. 2008;141(4):461–469.PubMedGoogle Scholar
  7. 7.
    Cheroutre H, Lambolez F. The thymus chapter in the life of gut-specific intra epithelial lymphocytes. Curr Opin Immunol. 2008;20(2):185–191.PubMedGoogle Scholar
  8. 8.
    Xiong N, Raulet DH. Development and selection of gammadelta T cells. Immunol Rev. 2007;215:15–31.PubMedGoogle Scholar
  9. 9.
    Takihara Y, Tkachuk D, Michalopoulos E, et al. Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus. Proc Natl Acad Sci USA. 1988;85(16):6097–6101.PubMedGoogle Scholar
  10. 10.
    Foroni L, Foldi J, Matutes E, et al. Alpha, beta and gamma T-cell receptor genes: rearrangements correlate with haematological phenotype in T cell leukaemias. Br J Haematol. 1987;67(3):307–318.PubMedGoogle Scholar
  11. 11.
    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):313–318.PubMedGoogle Scholar
  12. 12.
    Morris S, Rosenwald A, Staudt L, Duyster J. Molecular genetic aspects of non-Hodgkin lymphomagenesis. In: Greer JP, Foerster J, Rodgers GM, et al., eds. Wintrobe’s Clinical Hematology. 12th ed. Philadelphia: Lippincott Williams and Wilkins; 2009.Google Scholar
  13. 13.
    Lewis HD, Leveridge M, Strack PR, et al. Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling. Chem Biol. 2007;14(2):209–219.PubMedGoogle Scholar
  14. 14.
    Leich E, Haralambieva E, Zettl A, et al. Tissue microarray-based screening for chromosomal breakpoints affecting the T-cell receptor gene loci in mature T-cell lymphomas. J Pathol. 2007;213(1):99–105.PubMedGoogle Scholar
  15. 14a.
    Feldman AL, Law M, Remstein ED, et al. Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia 2009;23:574–580.Google Scholar
  16. 15.
    Mathas S, Johrens K, Joos S, et al. Elevated NF-kappaB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas. Blood. 2005;106(13):4287–4293.PubMedGoogle Scholar
  17. 16.
    Petit B, Leroy K, Kanavaros P, et al. Expression of p53 protein in T- and natural killer-cell lymphomas is associated with some clinicopathologic entities but rarely related to p53 mutations. Hum Pathol. 2001;32(2):196–204.PubMedGoogle Scholar
  18. 17.
    Jung JT, Kim DH, Kwak EK, et al. Clinical role of Bcl-2, Bax, or p53 overexpression in peripheral T-cell lymphomas. Ann Hematol. 2006;85(9):575–581.PubMedGoogle Scholar
  19. 18.
    Yamada Y, Hatta Y, Murata K, et al. Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell leukemia. J Clin Oncol. 1997;15(5):1778–1785.PubMedGoogle Scholar
  20. 19.
    Yamada Y, Kamihira S. Inactivation of tumor suppressor genes and the progression of adult T-cell leukemia-lymphoma. Leuk Lymphoma. 2005;46(11):1553–1559.PubMedGoogle Scholar
  21. 20.
    Uner AH, Saglam A, Han U, Hayran M, Sungur A, Ruacan S. PTEN and p27 expression in mature T-cell and NK-cell neoplasms. Leuk Lymphoma. 2005;46(10):1463–1470.PubMedGoogle Scholar
  22. 21.
    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):4971–4982.PubMedGoogle Scholar
  23. 22.
    Ballester B, Ramuz O, Gisselbrecht C, et al. Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas. Oncogene. 2006;25(10):1560-1570.PubMedGoogle Scholar
  24. 23.
    Thompson MA, Stumph J, Henrickson SE, et al. Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas. Hum Pathol. 2005;36(5):494–504.PubMedGoogle Scholar
  25. 24.
    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):2156–2164.PubMedGoogle Scholar
  26. 25.
    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):3321–3329.PubMedGoogle Scholar
  27. 26.
    Jarrett RF. Viruses and lymphoma/leukemia. J Pathol. 2006;208(2):176–186.PubMedGoogle Scholar
  28. 27.
    Kanavaros P, De Bruin PC, Briere J, Meijer CJ, Gaulard P. Epstein-Barr virus (EBV) in extranodal T-cell non-Hodgkin’s lymphomas (T-NHL). Identification of nasal T-NHL as a distinct clinicopathological entity associated with EBV. Leuk Lymphoma. 1995;18(1–2):27–34.PubMedGoogle Scholar
  29. 28.
    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):4163–4169.PubMedGoogle Scholar
  30. 29.
    Arisawa K, Soda M, Endo S, et al. Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan. Int J Cancer. 2000;85(3):319–324.PubMedGoogle Scholar
  31. 30.
    Matsuoka M, Jeang KT. Human T-cell leukemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat Rev Cancer. 2007;7(4):270–280.PubMedGoogle Scholar
  32. 31.
    Karenko L, Hahtola S, Ranki A. Molecular cytogenetics in the study of cutaneous T-cell lymphomas (CTCL). Cytogenet Genome Res. 2007;118(2–4):353–361.PubMedGoogle Scholar
  33. 32.
    Mao X, Lillington DM, Czepulkowski B, Russell-Jones R, Young BD, Whittaker S. Molecular cytogenetic characterization of Sezary syndrome. Genes Chromosomes Cancer. 2003;36(3):250–260.PubMedGoogle Scholar
  34. 33.
    Karenko L, Sarna S, Kahkonen M, Ranki A. Chromosomal abnormalities in relation to clinical disease in patients with cutaneous T-cell lymphoma: a 5-year follow-up study. Br J Dermatol. 2003;148(1):55–64.PubMedGoogle Scholar
  35. 34.
    Assaf C, Hummel M, Steinhoff M, et al. Early TCR-beta and TCR-gamma PCR detection of T-cell clonality indicates minimal tumor disease in lymph nodes of cutaneous T-cell lymphoma: diagnostic and prognostic implications. Blood. 2005;105(2):503–510.PubMedGoogle Scholar
  36. 35.
    Fischer TC, Gellrich S, Muche JM, et al. Genomic aberrations and survival in cutaneous T cell lymphomas. J Invest Dermatol. 2004;122(3):579–586.PubMedGoogle Scholar
  37. 36.
    Karenko L, Hahtola S, Paivinen S, et al. Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue. Cancer Res. 2005;65(18):8101–8110.PubMedGoogle Scholar
  38. 37.
    Vermeer MH, van Doorn R, Dijkman R, et al. Novel and highly recurrent chromosomal alterations in Sezary syndrome. Cancer Res. 2008;68(8):2689–2698.PubMedGoogle Scholar
  39. 38.
    Stein H, Foss HD, Durkop H, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 2000;96(12):3681–3695.PubMedGoogle Scholar
  40. 39.
    Falini B, Pileri S, Zinzani PL, et al. ALK+ lymphoma: clinico-pathological findings and outcome. Blood. 1999;93(8):2697–2706.PubMedGoogle Scholar
  41. 40.
    Gascoyne RD, Aoun P, Wu D, et al. Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood. 1999;93(11):3913–3921.PubMedGoogle Scholar
  42. 41.
    Fraga M, Brousset P, Schlaifer D, et al. Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance. Am J Clin Pathol. 1995;103(1):82–89.PubMedGoogle Scholar
  43. 42.
    Kaneko Y, Frizzera G, Edamura S, et al. A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis. Blood. 1989;73(3):806–813.PubMedGoogle Scholar
  44. 43.
    Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263(5151):1281–1284.PubMedGoogle Scholar
  45. 44.
    Li R, Morris SW. Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. Med Res Rev. 2008;28(3):372–412.PubMedGoogle Scholar
  46. 45.
    Lamant L, Dastugue N, Pulford K, Delsol G, Mariame B. A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Blood. 1999;93(9):3088–3095.PubMedGoogle Scholar
  47. 46.
    Hernandez L, Pinyol M, Hernandez S, et al. TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations. Blood. 1999;94(9):3265–3268.PubMedGoogle Scholar
  48. 47.
    Tort F, Pinyol M, Pulford K, et al. Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma. Lab Invest. 2001;81(3):419–426.PubMedGoogle Scholar
  49. 48.
    Gascoyne RD, Lamant L, Martin-Subero JI, et al. ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases. Blood. 2003;102(7):2568–2573.PubMedGoogle Scholar
  50. 49.
    Arrowsmith ER, Macon WR, Kinney MC, et al. Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification. Leuk Lymphoma. 2003;44(2):241–249.PubMedGoogle Scholar
  51. 50.
    Suzuki R, Kagami Y, Takeuchi K, et al. Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype. Blood. 2000;96(9):2993–3000.PubMedGoogle Scholar
  52. 51.
    Schlette EJ, Medeiros LJ, Goy A, Lai R, Rassidakis GZ. Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma. J Clin Oncol. 2004;22(9):1682–1688.PubMedGoogle Scholar
  53. 52.
    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.PubMedGoogle Scholar
  54. 53.
    Lai R, Rassidakis GZ, Lin Q, Atwell C, Medeiros LJ, Amin HM. Jak3 activation is significantly associated with ALK expression in anaplastic large cell lymphoma. Hum Pathol. 2005;36(9):939–944.PubMedGoogle Scholar
  55. 54.
    Slupianek A, Nieborowska-Skorska M, Hoser G, et al. Role of phosphatidylinositol 3-kinase-Akt pathway in nucleophosmin/anaplastic lymphoma kinase-mediated lymphomagenesis. Cancer Res. 2001;61(5):2194–2199.PubMedGoogle Scholar
  56. 55.
    Zamo A, Chiarle R, Piva R, et al. Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death. Oncogene. 2002;21(7):1038–1047.PubMedGoogle Scholar
  57. 56.
    Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications. Curr Opin Hematol. 2007;14(4):348–353.PubMedGoogle Scholar
  58. 57.
    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):4952–4963.PubMedGoogle Scholar
  59. 58.
    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):10703–10710.PubMedGoogle Scholar
  60. 59.
    Zhao WL, Mourah S, Mounier N, et al. 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. 2004;84(11):1512–1519.PubMedGoogle Scholar
  61. 60.
    Thorns C, Bastian B, Pinkel D, et al. Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: a matrix-based CGH approach. Genes Chromosomes Cancer. 2007;46(1):37–44.PubMedGoogle Scholar
  62. 61.
    Feller AC, Griesser H, Schilling CV, et al. Clonal gene rearrangement patterns correlate with immunophenotype and clinical parameters in patients with angioimmunoblastic lymphadenopathy. Am J Pathol. 1988;133(3):549–556.PubMedGoogle Scholar
  63. 62.
    Tan BT, Warnke RA, Arber DA. The frequency of B- and T-cell gene rearrangements and Epstein-Barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations. J Mol Diagn. 2006;8(4):466–475.PubMedGoogle Scholar
  64. 63.
    Mourad N, Mounier N, Briere J, et al. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials. Blood. 2008;111(9):4463–4470.PubMedGoogle Scholar
  65. 64.
    Caligiuri MA. Human natural killer cells. Blood. 2008;112(3):461–469.PubMedGoogle Scholar
  66. 65.
    Liang X, Graham DK. Natural killer cell neoplasms. Cancer. 2008;112(7):1425–1436.PubMedGoogle Scholar
  67. 66.
    Ishii H, Ogino T, Berger C, et al. Clinical usefulness of serum EBV DNA levels of BamHI W and LMP1 for Nasal NK/T-cell lymphoma. J Med Virol. 2007;79(5):562–572.PubMedGoogle Scholar
  68. 67.
    Hsieh PP, Tung CL, Chan AB, et al. EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma. Am J Clin Pathol. 2007;128(4):579–584.PubMedGoogle Scholar
  69. 68.
    Hasserjian RP, Harris NL. NK-cell lymphomas and leukemias: a spectrum of tumors with variable manifestations and immunophenotype. Am J Clin Pathol. 2007;127(6):860–868.PubMedGoogle Scholar
  70. 69.
    Siu LL, Chan V, Chan JK, Wong KF, Liang R, Kwong YL. Consistent patterns of allelic loss in natural killer cell lymphoma. Am J Pathol. 2000;157(6):1803–1809.PubMedGoogle Scholar
  71. 70.
    Nakashima Y, Tagawa H, Suzuki R, et al. Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type. Genes Chromosomes Cancer. 2005;44(3):247–255.PubMedGoogle Scholar
  72. 71.
    Quintanilla-Martinez L, Kremer M, Keller G, 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):2095–2105.PubMedGoogle Scholar
  73. 72.
    Aozasa K, Takakuwa T, Hongyo T, Yang WI. Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol. 2008;87(2):110–117.PubMedGoogle Scholar
  74. 73.
    Takahara M, Kishibe K, Bandoh N, Nonaka S, Harabuchi Y. P53, N- and K-Ras, and beta-catenin gene mutations and prognostic factors in nasal NK/T-cell lymphoma from Hokkaido, Japan. Hum Pathol. 2004;35(1):86–95.PubMedGoogle Scholar
  75. 74.
    Sakajiri S, Kawamata N, Egashira M, Mori K, Oshimi K. Molecular analysis of tumor suppressor genes, Rb, p53, p16INK4A, p15INK4B and p14ARF in natural killer cell neoplasms. Jpn J Cancer Res. 2001;92(10):1048–1056.PubMedGoogle Scholar
  76. 75.
    Kawamata N, Inagaki N, Mizumura S, et al. Methylation status analysis of cell cycle regulatory genes (p16INK4A, p15INK4B, p21Waf1/Cip1, p27Kip1 and p73) in natural killer cell disorders. Eur J Haematol. 2005;74(5):424–429.PubMedGoogle Scholar
  77. 76.
    Takakuwa T, Dong Z, Nakatsuka S, et al. Frequent mutations of Fas gene in nasal NK/T cell lymphoma. Oncogene. 2002;21(30):4702–4705.PubMedGoogle Scholar
  78. 77.
    Liu A, Takakuwa T, Luo WJ, Fujita S, Aozasa K. Alterations in ATR in nasal NK/T-cell lymphoma and chronic active Epstein-Barr virus infection. Cancer Sci. 2006;97(7):605–610.PubMedGoogle Scholar
  79. 78.
    Suzuki R, Takeuchi K, Ohshima K, Nakamura S. Extranodal NK/T-cell lymphoma: diagnosis and treatment cues. Hematol Oncol. 2008;26(2):66–72.PubMedGoogle Scholar
  80. 79.
    Lee J, Park YH, Kim WS, et al. Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors for risk-based stratification of therapy. Eur J Cancer. 2005;41(10):1402–1408.PubMedGoogle Scholar
  81. 80.
    Wang B, Li XQ, Ma X, Hong X, Lu H, Guo Y. Immunohistochemical expression and clinical significance of P-glycoprotein in previously untreated extranodal NK/T-cell lymphoma, nasal type. Am J Hematol. 2008;83(10):795-799.PubMedGoogle Scholar
  82. 81.
    Kwong YL. Natural killer-cell malignancies: diagnosis and treatment. Leukemia. 2005;19(12):2186–2194.PubMedGoogle Scholar
  83. 82.
    Yong W, Zheng W, Zhu J, et al. Midline NK/T-cell lymphoma nasal-type: treatment outcome, the effect of L-asparaginase based regimen, and prognostic factors. Hematol Oncol. 2006;24(1):28–32.PubMedGoogle Scholar
  84. 83.
    Suzuki R, Suzumiya J, Nakamura S, et al. Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia. 2004;18(4):763–770.PubMedGoogle Scholar
  85. 84.
    Ruskova A, Thula R, Chan G. Aggressive Natural Killer-Cell Leukemia: report of five cases and review of the literature. Leuk Lymphoma. 2004;45(12):2427–2438.PubMedGoogle Scholar
  86. 85.
    Przybylski GK, Wu H, Macon WR, et al. Hepatosplenic and subcutaneous panniculitis-like gamma/delta T cell lymphomas are derived from different Vdelta subsets of gamma/delta T lymphocytes. J Mol Diagn. 2000;2(1):11–19.PubMedGoogle Scholar
  87. 86.
    Willemze R, Jansen PM, Cerroni L, et al. Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases. Blood. 2008;111(2):838–845.PubMedGoogle Scholar
  88. 87.
    Rezania D, Sokol L, Cualing HD. Classification and treatment of rare and aggressive types of peripheral T-cell/natural killer-cell lymphomas of the skin. Cancer Control. 2007;14(2):112–123.PubMedGoogle Scholar
  89. 88.
    Farcet JP, Gaulard P, Marolleau JP, et al. Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta. Blood. 1990;75(11):2213–2219.PubMedGoogle Scholar
  90. 89.
    Weidmann E. Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990. Leukemia. 2000;14(6): 991–997.PubMedGoogle Scholar
  91. 90.
    Belhadj K, Reyes F, Farcet JP et al. Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood. 2003;102(13):4261–4269.PubMedGoogle Scholar
  92. 91.
    Jaffe ES. Pathobiology of peripheral T-cell lymphomas. Hematology Am Soc Hematol Educ Program. 2006:317–322.Google Scholar
  93. 92.
    Macon WR, Levy NB, Kurtin PJ, et al. Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas. Am J Surg Pathol. 2001;25(3):285–296.PubMedGoogle Scholar
  94. 93.
    Gale J, Simmonds PD, Mead GM, Sweetenham JW, Wright DH. Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol. 2000;18(4):795–803.PubMedGoogle Scholar
  95. 94.
    Al-Toma A, Verbeek WH, Hadithi M, von Blomberg BM, Mulder CJ. Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Gut. 2007;56(10):1373–1378.PubMedGoogle Scholar
  96. 95.
    Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357(17):1731–1743.PubMedGoogle Scholar
  97. 96.
    de Mascarel A, Belleannee G, Stanislas S, et al. Mucosal intraepithelial T-lymphocytes in refractory celiac disease: a neoplastic population with a variable CD8 phenotype. Am J Surg Pathol. 2008;32(5):744–751.PubMedGoogle Scholar
  98. 97.
    Obermann EC, Diss TC, Hamoudi RA, et al. Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma. J Pathol. 2004;202(2):252–262.PubMedGoogle Scholar
  99. 98.
    Zettl A, Ott G, Makulik A, et al. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma. Am J Pathol. 2002;161(5):1635–1645.PubMedGoogle Scholar
  100. 99.
    Baumgartner AK, Zettl A, Chott A, Ott G, Muller-Hermelink HK, Starostik P. High frequency of genetic aberrations in enteropathy-type T-cell lymphoma. Lab Invest. 2003;83(10):1509–1516.PubMedGoogle Scholar
  101. 100.
    Quintanilla-Martinez L, Lome-Maldonado C, Ott G, et al. Primary intestinal non-Hodgkin’s lymphoma and Epstein-Barr virus: high frequency of EBV-infection in T-cell lymphomas of Mexican origin. Leuk Lymphoma. 1998;30(1–2):111–121.PubMedGoogle Scholar
  102. 101.
    Dearden CE. T-cell prolymphocytic leukemia. Med Oncol. 2006;23(1):17–22.PubMedGoogle Scholar
  103. 102.
    Matutes E, Brito-Babapulle V, Swansbury J, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood. 1991;78(12):3269–3274.PubMedGoogle Scholar
  104. 103.
    Foucar K. Mature T-cell leukemias including T-prolymphocytic leukemia, adult T-cell leukemia/lymphoma, and Sezary syndrome. Am J Clin Pathol. 2007;127(4):496–510.PubMedGoogle Scholar
  105. 104.
    Noguchi M, Ropars V, Roumestand C, Suizu F. Proto-oncogene TCL1: more than just a coactivator for Akt. FASEB J. 2007;21(10):2273–2284.PubMedGoogle Scholar
  106. 105.
    Durig J, Bug S, Klein-Hitpass L, et al. Combined single nucleotide polymorphism-based genomic mapping and global gene expression profiling identifies novel chromosomal imbalances, mechanisms and candidate genes important in the pathogenesis of T-cell prolymphocytic leukemia with inv(14)(q11q32). Leukemia. 2007;21(10):2153–2163.PubMedGoogle Scholar
  107. 106.
    Usui T, Yanagihara K, Tsukasaki K, et al. Characteristic expression of HTLV-1 basic zipper factor (HBZ) transcripts in HTLV-1 provirus-positive cells. Retrovirology. 2008;5:34.PubMedGoogle Scholar
  108. 107.
    Taylor GP, Matsuoka M. Natural history of adult T-cell leukemia/lymphoma and approaches to therapy. Oncogene. 2005;24(39):6047–6057.PubMedGoogle Scholar
  109. 108.
    Mesnard JM, Barbeau B, Devaux C. HBZ, a new important player in the mystery of adult T-cell leukemia. Blood. 2006;108(13):3979–3982.PubMedGoogle Scholar
  110. 109.
    Kamada N, Sakurai M, Miyamoto K, et al. Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report. Cancer Res. 1992;52(6):1481–1493.PubMedGoogle Scholar
  111. 110.
    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):4500–4507.PubMedGoogle Scholar
  112. 111.
    Hidaka T, Nakahata S, Hatakeyama K, et al. Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma. Blood. 2008;112(2):383–393.PubMedGoogle Scholar
  113. 112.
    Hatta Y, Koeffler HP. Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL). Leukemia. 2002;16(6):1069–1085.PubMedGoogle Scholar
  114. 113.
    Roncador G, Garcia JF, Garcia JF, et al. FOXP3, a selective marker for a subset of adult T-cell leukemia/lymphoma. Leukemia. 2005;19(12):2247–2253.PubMedGoogle Scholar
  115. 114.
    Karube K, Aoki R, Sugita Y, et al. The relationship of FOXP3 expression and clinicopathological characteristics in adult T-cell leukemia/lymphoma. Mod Pathol. 2008;21(5):617–625.PubMedGoogle Scholar
  116. 115.
    Yoshie O, Fujisawa R, Nakayama T, et al. Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells. Blood. 2002;99(5):1505–1511.PubMedGoogle Scholar
  117. 116.
    Choi YL, Tsukasaki K, O’Neill MC, et al. A genomic analysis of adult T-cell leukemia. Oncogene. 2007;26(8):1245–1255.PubMedGoogle Scholar
  118. 117.
    Itoyama T, Chaganti RS, Yamada Y, et al. Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki. Blood. 2001;97(11):3612–3620.PubMedGoogle Scholar
  119. 118.
    Besson C, Panelatti G, Delaunay C, et al. Treatment of adult T-cell leukemia-lymphoma by CHOP followed by therapy with antinucleosides, alpha interferon and oral etoposide. Leuk Lymphoma. 2002;43(12):2275–2279.PubMedGoogle Scholar
  120. 119.
    Waldmann TA. Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. Oncogene. 2007;26(25):3699–3703.PubMedGoogle Scholar
  121. 120.
    Fukushima T, Miyazaki Y, Honda S, et al. Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma. Leukemia. 2005;19(5):829–834.PubMedGoogle Scholar
  122. 121.
    Shah MV, Zhang R, Irby R, et al. Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes. Blood. 2008;112(3):770–781.PubMedGoogle Scholar
  123. 122.
    Epling-Burnette PK, Liu JH, Catlett-Falcone R, et al. Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest. 2001;107(3):351–362.PubMedGoogle Scholar
  124. 123.
    Paolo C, Lucia F, Anna D. Hematopoietic stem cell transplantation in peripheral T-cell lymphomas. Leuk Lymphoma. 2007;48(8):1496–1501.PubMedGoogle Scholar
  125. 124.
    Rezania D, Cualing HD, Ayala E. The diagnosis, management, and role of hematopoietic stem cell transplantation in aggressive peripheral T-cell neoplasms. Cancer Control. 2007;14(2):151–159.PubMedGoogle Scholar
  126. 125.
    Chen AI, Advani RH. Beyond the guidelines in the treatment of peripheral T-cell lymphoma: new drug development. J Natl Compr Canc Netw. 2008;6(4):428–435.PubMedGoogle Scholar
  127. 126.
    Dang NH, Pro B, Hagemeister FB, et al. Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma. Br J Haematol. 2007;136(3):439–447.PubMedGoogle Scholar
  128. 127.
    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):2920–2924.PubMedGoogle Scholar
  129. 128.
    Zinzani PL, Alinari L, Tani M, Fina M, Pileri S, Baccarani M. Preliminary observations of a phase II study of reduced-dose alemtuzumab treatment in patients with pretreated T-cell lymphoma. Haematologica. 2005;90(5):702–703.PubMedGoogle Scholar
  130. 129.
    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):4655–4662.PubMedGoogle Scholar
  131. 130.
    Casale DA, Bartlett NL, Hurd DD, et al. A phase I open label dose escalation study to evaluate MEDI-507 in patients with CD2-positive T-cell lymphoma/leukemia. Blood. 2006;108:771a.Google Scholar
  132. 131.
    Forero-Torres A, Bernstein SH, Gopal A, et al. SGN-30 (Anti-CD30 mAb) has a single-agent response rate of 21% in patients with refractory or recurrent systemic anaplastic large cell lymphoma (ALCL). Blood. 2006;108:768a.Google Scholar
  133. 132.
    Ansell SM, Horwitz SM, Engert A, et al. Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin’s lymphoma and anaplastic large-cell lymphoma. J Clin Oncol. 2007;25(19):2764–2769.PubMedGoogle Scholar
  134. 133.
    Uike N, Tsukasaki K, Utsunomiya A, et al. Phase I study of KW-0761, a humanized anti-CCR4 antibody, in patients (pts) with relapsed or refractory adult T-cell leukemia-lymphoma (ATLL) and peripheral T-cell lymphoma (PTCL) preliminary results. Blood. 2007;110:194b.Google Scholar
  135. 134.
    O’Conner OA, Hamlin PA, Gerecitano J, et al. Pralatrexate (PDX) produces durable complete remissions in patients with chemotherapy resistant precursor and peripheral T-cell lymphomas: results of the MSKCC phase I/II experience. Blood. 2006;108:122a–123a.Google Scholar
  136. 135.
    Newbold A, Lindemann RK, Cluse LA, Whitecross KF, Dear AE, Johnstone RW. Characterisation of the novel apoptotic and therapeutic activities of the histone deacetylase inhibitor romidepsin. Mol Cancer Ther. 2008;7(5):1066–1079.PubMedGoogle Scholar
  137. 136.
    Ellis L, Pan Y, Smyth GK, et al. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma. Clin Cancer Res. 2008;14(14):4500–4510.PubMedGoogle Scholar
  138. 137.
    Packham G. The role of NF-kappaB in lymphoid malignancies. Br J Haematol. 2008;143(1):3–15.PubMedGoogle Scholar
  139. 138.
    Querfeld C, Rizvi MA, Kuzel TM, et al. The selective protein kinase C beta inhibitor enzastaurin induces apoptosis in cutaneous T-cell lymphoma cell lines through the AKT pathway. J Invest Dermatol. 2006;126(7):1641–1647.PubMedGoogle Scholar
  140. 139.
    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):1160–1167.PubMedGoogle Scholar
  141. 140.
    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 prepublished.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • John P. Greer
    • 1
  • Utpal P. Davé
    • 2
  • Nishitha Reddy
    • 3
  • Christine M. Lovly
    • 4
  • Claudio A. Mosse
    • 5
  1. 1.Department of Hematology/Stem Cell TransplantationVanderbilt University Medical CenterNashvilleUSA
  2. 2.Division of Hematology/OncologyVanderbilt University Medical CenterNashvilleUSA
  3. 3.Department of MedicineVanderbilt University Medical CenterNashvilleUSA
  4. 4.Department of Hematology and OncologyVanderbilt University School of MedicineNashvilleUSA
  5. 5.Department of PathologyVanderbilt University Medical Center and Nashville Veterans Administration Medical Center, Tennessee Valley Healthcare SystemsNashvilleUSA

Personalised recommendations