Current Hematologic Malignancy Reports

, Volume 2, Issue 4, pp 257–264 | Cite as

Adult T-cell leukemia/lymphoma and HTLV-1

  • Renaud Mahieux
  • Antoine GessainEmail author


Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered, more than 25 years ago. HTLV-1 infects 15 to 20 million individuals worldwide. This oncoretrovirus can be transmitted in three ways: horizontally (sexually), vertically (mother to child), and via blood transfusion. HTLV-1 causes two major diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). ATLL can be classified into four major subtypes: a smoldering type, a chronic type, a lymphoma type, and a leukemic type. Because of intrinsic chemoresistance and severe immunosuppression, the survival rate of ATLL patients, especially those who develop the acute leukemic or lymphoma forms, is very poor, and such clonal malignant CD4 expansion remains one of the most severe lymphoproliferations. This article discusses a number of recent treatments including antiretroviral therapy, aggressive chemotherapy, and allogeneic bone-marrow transplantation, as well as new drugs.


Alemtuzumab Arsenic Trioxide Proviral Load ATLL Cell ATLL Patient 
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.


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References and Recommended Reading

  1. 1.
    Poiesz BJ, Ruscetti FW, Gazdar AF, et al.: Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A 1980, 77:7415–7419.PubMedCrossRefGoogle Scholar
  2. 2.
    Takatsuki T: Adult T-cell leukemia in Japan. In Topics in Hematology. Edited by Seno S, Takaku F, Irino S. Amsterdam: Exerpta Medica; 1977:73–77.Google Scholar
  3. 3.
    Yoshida M, Miyoshi I, Hinuma Y: Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A 1982, 79:2031–2035.PubMedCrossRefGoogle Scholar
  4. 4.
    Proietti FA, Carneiro-Proietti AB, Catalan-Soares BC, Murphy EL: Global epidemiology of HTLV-I infection and associated diseases. Oncogene 2005, 24:6058–6068.PubMedCrossRefGoogle Scholar
  5. 5.
    Gessain A: Epidemiology of HTLV-1. In Human T-Cell Lymphotropic Virus Type 1. Edited by Holsberg P, Hatler D. Chichester, England: John Wiley & Sons; 1996:34–63.Google Scholar
  6. 6.
    Ureta-Vidal A, Angelin-Duclos C, Tortevoye P, et al.: Mother-to-child transmission of human T-cell-leukemia/lymphoma virus type I: implication of high antiviral antibody titer and high proviral load in carrier mothers. Int J Cancer 1999, 82:832–836.PubMedCrossRefGoogle Scholar
  7. 7.
    Roucoux DF, Wang B, Smith D, et al.: A prospective study of sexual transmission of human T lymphotropic virus (HTLV)-I and HTLV-II. J Infect Dis 2005, 191:1490–1497.PubMedCrossRefGoogle Scholar
  8. 8.
    Manns A, Murphy EL, Wilks R, et al.: Detection of early human T-cell lymphotropic virus type I antibody patterns during seroconversion among transfusion recipients. Blood 1991, 77:896–905.PubMedGoogle Scholar
  9. 9.
    Wattel E, Vartanian JP, Pannetier C, Wain-Hobson S: Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy. J Virol 1995, 69:2863–2868.PubMedGoogle Scholar
  10. 10.
    Verdonck K, Gonzalez E, Van Dooren S, et al.: Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis 2007, 7:266–281.PubMedCrossRefGoogle Scholar
  11. 11.
    Gerard Y, Lepere JF, Pradinaud R, et al.: Clustering and clinical diversity of adult T-cell leukemia/lymphoma associated with HTLV-I in a remote black population of French Guiana. Int J Cancer 1995, 60:773–776.PubMedCrossRefGoogle Scholar
  12. 12.
    Hanchard B: Adult T-cell leukemia/lymphoma in Jamaica: 1986–1995. J Acquir Immune Defic Syndr Hum Retrovirol 1996, 13:S20–S25.PubMedCrossRefGoogle Scholar
  13. 13.
    Pombo De Oliveira MS, Loureiro P, Bittencourt A, et al.: Geographic diversity of adult T-cell leukemia/lymphoma in Brazil. The Brazilian ATLL Study Group. Int J Cancer 1999, 83:291–298.PubMedCrossRefGoogle Scholar
  14. 14.
    The third nation-wide study on adult T-cell leukemia/lymphoma (ATL) in Japan: characteristic patterns of HLA antigen and HTLV-I infection in ATL patients and their relatives. The T-and B-cell Malignancy Study Group. Int J Cancer 1988, 41:505–512.CrossRefGoogle Scholar
  15. 15.
    Murphy EL, Hanchard B, Figueroa JP, et al.: Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I. Int J Cancer 1989, 43:250–253.PubMedCrossRefGoogle Scholar
  16. 16.
    Takatsuki K, Yamaguchi K, Matsuoka M: Adult T-cell leukemia. In Human T-Cell Lymphotropic Virus type 1. Edited by Holsberg P, Hatler D. Chichester, England: John Wiley & Sons; 1996:219–246.Google Scholar
  17. 17.
    Shimoyama M: Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymhoma. A report from the Lymphoma Study Group (1984–87). Br J Haematol 1991, 79:428–437.PubMedGoogle Scholar
  18. 18.
    Shimoyama M: Treatment of patients with adult T-cell leukemia-lymphoma: an overview. In Advances in Adult T-cell Leukemia and HTLV-1 Research. Edited by Takatsuki K, Hinuma Y, Yoshida M. Tokyo: Japan Scientific Societies Press; 1992:43–46.Google Scholar
  19. 19.
    Yamaguchi K, Nishimura H, Kohrogi H, et al.: A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases. Blood 1983, 62:758–766.PubMedGoogle Scholar
  20. 20.
    Yamaguchi K, Yoshioka R, Kiyokawa T, et al.: Lymphoma type adult T-cell leukemia—a clinicopathologic study of HTLV related T-cell type malignant lymphoma. Hematol Oncol 1986, 4:59–65.PubMedCrossRefGoogle Scholar
  21. 21.
    Levine PH, Cleghorn F, Manns A, et al.: Adult T-cell leukemia/lymphoma: a working point-score classification for epidemiological studies. Int J Cancer 1994, 59:491–493.PubMedCrossRefGoogle Scholar
  22. 22.
    Chen S, Ishii N, Ine S, et al.: Regulatory T cell-like activity of Foxp3+ adult T cell leukemia cells. Int Immunol 2006, 18:269–277.PubMedCrossRefGoogle Scholar
  23. 23.
    Yano H, Ishida T, Inagaki A, et al.: Regulatory T-cell function of adult T-cell leukemia/lymphoma cells. Int J Cancer 2007, 120:2052–2057.PubMedCrossRefGoogle Scholar
  24. 24.
    Shimoyama M, Sakurai M, Kamada N: Chromosomal aberrations in adult T-cell leukemia-lymphoma: summary of a karyotype review committee report. In Advances in Adult T-cell Leukemia and HTLV-1 Research. Edited by Takatsuki K, Hinuma Y, Yoshida M. Tokyo: Scientific Societies Press; 1992:95–105.Google Scholar
  25. 25.
    Sakashita A, Hattori T, Miller CW, et al.: Mutations of the p53 gene in adult T-cell leukemia. Blood 1992, 79:477–480.PubMedGoogle Scholar
  26. 26.
    Yamada Y, Kamihira S: Inactivation of tumor suppressor genes and the progression of adult T-cell leukemia-lymphoma. Leuk Lymphoma 2005, 46:1553–1559.PubMedCrossRefGoogle Scholar
  27. 27.
    Yoshida M, Seiki M, Yamaguchi K, Takatsuki K: Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci U S A 1984, 81:2534–2537.PubMedCrossRefGoogle Scholar
  28. 28.
    Kamihira S, Sugahara K, Tsuruda K, et al.: Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells. Clin Lab Haematol 2005, 27:235–241.PubMedCrossRefGoogle Scholar
  29. 29.
    Leclercq I, Mortreux F, Morschhauser F, et al.: Semiquantitative analysis of residual disease in patients treated for adult T-cell leukaemia/lymphoma (ATLL). Br J Haematol 1999, 105:743–751.PubMedCrossRefGoogle Scholar
  30. 30.
    Tannir N, Riggs S, Velasquez W, et al.: Hypercalcemia, unusual bone lesions, and human T-cell leukemia-lymphoma virus in adult T-cell lymphoma. Cancer 1985, 55:615–619.PubMedCrossRefGoogle Scholar
  31. 31.
    White JD, Zaknoen SL, Kasten-Sportes C, et al.: Infectious complications and immunodeficiency in patients with human T-cell lymphotropic virus I-associated adult T-cell leukemia/lymphoma. Cancer 1995, 75:1598–1607.PubMedCrossRefGoogle Scholar
  32. 32.
    Gabet AS, Mortreux F, Talarmin A, et al.: High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis. Oncogene 2000, 19:4954–4960.PubMedCrossRefGoogle Scholar
  33. 33.
    Matsuoka M, Jeang KT: Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat Rev Cancer 2007, 7:270–280.PubMedCrossRefGoogle Scholar
  34. 34.
    Afonso PV, Zamborlini A, Saib A, Mahieux R: Centro-some and retroviruses: the dangerous liaisons [review]. Retrovirology 2007, 4:27.PubMedCrossRefGoogle Scholar
  35. 35.
    Hanon E, Hall S, Taylor GP, et al.: Abundant Tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes. Blood 2000, 95:1386–1392.PubMedGoogle Scholar
  36. 36.
    Hanon E, Stinchcombe JC, Saito M, et al.: Fratricide among CD8(+) T lymphocytes naturally infected with human T cell lymphotropic virus type I. Immunity 2000, 13:657–664.PubMedCrossRefGoogle Scholar
  37. 37.
    Gaudray G, Gachon F, Basbous J, et al.: The complementary strand of the human T-cell leukemia virus type 1 RNA genome encodes a bZIP transcription factor that down-regulates viral transcription. J Virol 2002, 76:12813–12822.PubMedCrossRefGoogle Scholar
  38. 38.
    Satou Y, Yasunaga J, Yoshida M, Matsuoka M: HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. Proc Natl Acad Sci U S A 2006, 103:720–725.PubMedCrossRefGoogle Scholar
  39. 39.
    Mesnard JM, Barbeau B, Devaux C: HBZ, a new important player in the mystery of adult T-cell leukemia. Blood 2006, 108:3979–3982.PubMedCrossRefGoogle Scholar
  40. 40.
    Arnold J, Yamamoto B, Li M, et al.: Enhancement of infectivity and persistence in vivo by HBZ, a natural antisense coded protein of HTLV-1. Blood 2006, 107:3976–3982.PubMedCrossRefGoogle Scholar
  41. 41.
    Bazarbachi A, Ghez D, Lepelletier Y, et al.: New therapeutic approaches for adult T-cell leukaemia. Lancet Oncol 2004, 5:664–672.PubMedCrossRefGoogle Scholar
  42. 42.
    Tsukasaki K, Utsunomiya A, Fukuda H, et al.: Clinical trials for the treatment of ATLL by the Japan Clinical Oncology Group (JCOG) [abstract]. AIDS Res Hum Retroviruses 2007, 23:592–593.Google Scholar
  43. 43.
    Hermine O, Panelatti G, Ramos J, et al.: A worldwide meta-analysis of the use of zidovudine and interferon alpha for the treatment of adult T-cell leukemia/lymphoma [abstract]. AIDS Res Hum Retroviruses 2007, 23:597–598.Google Scholar
  44. 44.
    Datta A, Bellon M, Sinha-Datta U, et al.: Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence. Blood 2006, 108:1021–1029.PubMedCrossRefGoogle Scholar
  45. 45.
    Ramos JC, Ruiz P Jr., Ratner L, et al.: IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma. Blood 2007, 109:3060–3068.PubMedCrossRefGoogle Scholar
  46. 46.
    Jeang KT, Giam CZ, Majone F, Aboud M: Life, death, and Tax: role of HTLV-I oncoprotein in genetic instability and cellular transformation. J Biol Chem 2004, 279:31991–31994.PubMedCrossRefGoogle Scholar
  47. 47.
    Mori N, Yamada Y, Ikeda S, et al.: Bay 11-7082 inhibits transcription factor NF-κB and induces apoptosis of HTLV-I-infected T-cell lines and primary adult T-cell leukemia cells. Blood 2002, 100:1828–1834.PubMedCrossRefGoogle Scholar
  48. 48.
    Nasr R, El-Sabban ME, Karam JA, et al.: Efficacy and mechanism of action of the proteasome inhibitor PS-341 in T-cell lymphomas and HTLV-I associated adult T-cell leukemia/lymphoma. Oncogene 2005, 24:419–430.PubMedCrossRefGoogle Scholar
  49. 49.
    Watanabe M, Ohsugi T, Shoda M, et al.: Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-κB, as a strategy for chemoprevention and therapy of adult T-cell leukemia. Blood 2005, 106:2462–2471.PubMedCrossRefGoogle Scholar
  50. 50.
    Ishitsuka K, Hanada S, Suzuki S, et al.: Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids. Br J Haematol 1998, 103:721–728.PubMedCrossRefGoogle Scholar
  51. 51.
    Bazarbachi A, El-Sabban ME, Nasr R, et al.: Arsenic trioxide and interferon-α synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-transformed cells. Blood 1999, 93:278–283.PubMedGoogle Scholar
  52. 52.
    El-Sabban ME, Nasr R, Dbaibo G, et al.: Arsenic-interferon-α-triggered apoptosis in HTLV-I transformed cells is associated with Tax down-regulation and reversal of NF-κB activation. Blood 2000, 96:2849–2855.PubMedGoogle Scholar
  53. 53.
    Mahieux R, Pise-Masison C, Gessain A, et al.: Arsenic trioxide induces apoptosis in human T-cell leukemia virus type 1-and type 2-infected cells by a caspase-3-dependent mechanism involving Bcl-2 cleavage. Blood 2001, 98:3762–3769.PubMedCrossRefGoogle Scholar
  54. 54.
    Hermine O, Dombret H, Poupon J, et al.: Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma. Hematol J 2004, 5:130–134.PubMedCrossRefGoogle Scholar
  55. 55.
    Waldmann TA: Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol 2007, 27:1–18.PubMedCrossRefGoogle Scholar
  56. 56.
    Moura IC, Lepelletier Y, Arnulf B, et al.: A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients. Blood 2004, 103:1838–1845.PubMedCrossRefGoogle Scholar
  57. 57.
    Janik JE, Dunleavy KE, Pittaluga SE, et al.: A pilot trial of alemtuzumab (Campath-1H) and dose adjusted EPOCH (DA-EPOCH) in CD52-expressing aggressive T cell malignancies [abstract]. AIDS Res Hum Retroviruses 2007, 23:606.Google Scholar
  58. 58.
    Morris J, Sharma K, O’Mahony D, et al.: A phase II study of the efficacy and toxicity of alemtuzumab (Campath) for treatment of HTLV-1-associated ATL [abstract]. AIDS Res Hum Retroviruses 2007, 23:632–633.Google Scholar
  59. 59.
    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, 19:829–834.PubMedCrossRefGoogle Scholar
  60. 60.
    Kannagi M, Harashima N, Kurihara K, et al.: Tumor immunity against adult T-cell leukemia. Cancer Sci 2005, 96:249–255.PubMedCrossRefGoogle Scholar
  61. 61.
    Okamura J, Utsunomiya A, Tanosaki R, et al.: Allogeneic stem-cell transplantation with reduced conditioning intensity as a novel immunotherapy and antiviral therapy for adult T-cell leukemia/lymphoma. Blood 2005, 105:4143–4145.PubMedCrossRefGoogle Scholar
  62. 62.
    Tanosaki R, Kim S, Fukuda T, et al.: Reduced intensity stem cell transplantation is relatively safe and effective in patients with ATLL [abstract]. AIDS Res Hum Retroviruses 2007, 23:592.Google Scholar
  63. 63.
    Mahieux R, Gessain A: HTLV-1 and associated adult T-cell leukemia/lymphoma [review]. Rev Clin Exp Hematol 2003, 7:336–361.PubMedGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Department of Virology, Institut PasteurUnité d’Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 3015Paris Cedex 15France

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