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Viruses
06, 2011;3 (6): 886-900.

Targeting HTLV-1 activation of NFκB in mouse models and ATLL patients.

Daniel A Rauch, Lee Ratner
Author Information
  1. Daniel A Rauch: Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA. drauch@dom.wustl.edu
PMID: 21994759 DOI: 10.3390/v3060886

Abstract

Of the millions of HTLV-1 infected carriers worldwide, 3-5% will develop an aggressive T-cell neoplasm that is highly refractory to conventional therapy. The virus carries the Tax oncogene which constitutively activates the NFκB pathway. This co-option of signaling through NFκB provides for the HTLV-1 infected cell an escape from cell cycle arrest and apoptosis, a steady source of growth factors, and a mechanism by which the virus can activate its own target cell. Therapies that target the NFκB pathway sensitize adult T-cell leukemia/lymphoma (ATLL) cells to apoptosis. A focus on translational interrogation of NFκB inhibitors in animal models and ATLL patients is needed to advance NFκB-targeted ATLL therapies to the bedside.

Keywords

ATLL therapy HTLV-1 NFκB mouse models tax

References

  1. Blood. 2004 Nov 15;104(10):3305-11 [PMID: 15292059]
  2. J Exp Med. 2010 Dec 20;207(13):2785-92 [PMID: 21135137]
  3. Mol Cell Biol. 1991 Sep;11(9):4635-41 [PMID: 1875943]
  4. EMBO J. 2001 Dec 3;20(23):6805-15 [PMID: 11726516]
  5. Nat Med. 2007 May;13(5):527-8 [PMID: 17479090]
  6. Blood. 2005 Dec 15;106(13):4294-302 [PMID: 16118323]
  7. Nat Rev Mol Cell Biol. 2008 Aug;9(8):628-38 [PMID: 18628784]
  8. Br J Haematol. 1991 Nov;79(3):428-37 [PMID: 1751370]
  9. Virology. 1998 Sep 1;248(2):332-41 [PMID: 9721242]
  10. Immunol Res. 2006;34(1):1-12 [PMID: 16720895]
  11. Arthritis Rheum. 1993 Nov;36(11):1612-20 [PMID: 8240438]
  12. J Clin Invest. 1996 Jul 15;98(2):271-8 [PMID: 8755634]
  13. J Virol. 2001 Mar;75(5):2185-93 [PMID: 11160722]
  14. Oncogene. 1995 Mar 16;10(6):1045-51 [PMID: 7700628]
  15. AIDS Res Hum Retroviruses. 2010 May;26(5):593-603 [PMID: 20438380]
  16. Blood. 2004 Aug 1;104(3):802-9 [PMID: 15090453]
  17. PLoS One. 2009;4(2):e4420 [PMID: 19204798]
  18. Science. 1987 Sep 11;237(4820):1340-3 [PMID: 2888191]
  19. Front Biosci (Landmark Ed). 2009 Jan 01;14:3338-51 [PMID: 19273278]
  20. Blood. 2009 Feb 12;113(7):1493-500 [PMID: 18971418]
  21. Oncogene. 1999 Nov 22;18(49):6948-58 [PMID: 10602469]
  22. Virology. 1993 Sep;196(1):309-18 [PMID: 8356801]
  23. J Biol Chem. 2005 Oct 21;280(42):35713-22 [PMID: 16105841]
  24. Nutr Cancer. 2005;52(2):189-201 [PMID: 16201850]
  25. PLoS One. 2011 Apr 01;6(4):e18518 [PMID: 21483764]
  26. Retrovirology. 2009 Dec 17;6:116 [PMID: 20017942]
  27. J Virol. 1989 Jul;63(7):3185-9 [PMID: 2724422]
  28. Virology. 1993 Nov;197(1):196-204 [PMID: 8212554]
  29. Blood. 2001 Aug 15;98(4):1200-8 [PMID: 11493471]
  30. Nat Med. 2009 Apr;15(4):455-61 [PMID: 19305414]
  31. Virology. 1994 Nov 1;204(2):656-64 [PMID: 7941334]
  32. Int Rev Immunol. 2007 Sep-Dec;26(5-6):269-81 [PMID: 18027201]
  33. PLoS One. 2010 Dec 30;5(12):e15755 [PMID: 21209895]
  34. Mol Cell Biol. 1991 Oct;11(10):5222-8 [PMID: 1922042]
  35. Am J Pathol. 1992 Jun;140(6):1401-10 [PMID: 1605307]
  36. Oncogene. 2005 Sep 5;24(39):6035-46 [PMID: 16155610]
  37. J Biol Chem. 2005 Dec 9;280(49):40965-73 [PMID: 16207722]
  38. J Pathol. 1998 Oct;186(2):209-14 [PMID: 9924438]
  39. Antimicrob Agents Chemother. 2011 May;55(5):2011-7 [PMID: 21343468]
  40. Science. 1987 Sep 11;237(4820):1324-9 [PMID: 2888190]
  41. J Biol Chem. 2004 Apr 30;279(18):18137-45 [PMID: 14963024]
  42. Nature. 2008 Jul 24;454(7203):436-44 [PMID: 18650914]
  43. Curr Top Microbiol Immunol. 1990;160:121-8 [PMID: 2191838]
  44. Blood. 1995 Apr 1;85(7):1865-70 [PMID: 7703492]
  45. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9220-5 [PMID: 16751281]
  46. Leuk Res. 2008 Feb;32(2):287-96 [PMID: 17644177]
  47. Nature. 1989 Sep 7;341(6237):72-4 [PMID: 2788824]
  48. J Clin Oncol. 2009 Jan 20;27(3):453-9 [PMID: 19064971]
  49. Blood. 2002 Sep 1;100(5):1828-34 [PMID: 12176906]
  50. Mol Cell Biol. 1994 Aug;14(8):5371-83 [PMID: 8035815]
  51. Blood. 2009 Sep 24;114(13):2709-20 [PMID: 19584402]
  52. Am J Pathol. 1989 Dec;135(6):1025-33 [PMID: 2688429]
  53. Blood. 2009 Oct 1;114(14):2961-8 [PMID: 19657116]
  54. J Exp Med. 1997 Jul 7;186(1):57-64 [PMID: 9206997]
  55. Science. 1992 Dec 11;258(5089):1792-5 [PMID: 1299224]
  56. Mol Cell Biol. 2000 May;20(10):3377-86 [PMID: 10779327]
  57. Int J Cancer. 2006 Feb 1;118(3):765-72 [PMID: 16106398]
  58. Blood. 2011 Mar 24;117(12):3363-9 [PMID: 21212284]
  59. J Immunol. 1995 Aug 1;155(3):1588-98 [PMID: 7636219]
  60. Blood. 1997 Jul 15;90(2):783-94 [PMID: 9226179]
  61. Mol Cancer Ther. 2005 Apr;4(4):578-86 [PMID: 15827331]
  62. Science. 1991 Aug 30;253(5023):1026-8 [PMID: 1887217]
  63. J Virol. 1999 Jun;73(6):4856-65 [PMID: 10233947]
  64. Mol Cancer Ther. 2006 Mar;5(3):704-12 [PMID: 16546985]
  65. Oncogene. 2005 Oct 6;24(44):6719-28 [PMID: 16007163]
  66. Oncogene. 1992 Dec;7(12):2399-405 [PMID: 1461648]
  67. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1057-61 [PMID: 7862633]
  68. Nat Med. 2006 Apr;12(4):466-72 [PMID: 16550188]
  69. Carcinogenesis. 2005 Aug;26(8):1382-8 [PMID: 15831528]
  70. J Virol. 1996 May;70(5):3280-5 [PMID: 8627811]
  71. Retrovirology. 2009 Sep 17;6:83 [PMID: 19761585]
  72. J Immunol. 1999 Mar 1;162(5):2956-63 [PMID: 10072546]
  73. Cell Res. 2011 Jan;21(1):86-102 [PMID: 21102550]

Grants

  1. P50 CA094056/NCI NIH HHS
  2. CA63417/NCI NIH HHS
  3. CA 10073/NCI NIH HHS
  4. R01 CA063417/NCI NIH HHS
  5. CA94056/NCI NIH HHS

MeSH Term

Animals
Disease Models, Animal
Gene Products, tax
Human T-lymphotropic virus 1
Humans
Leukemia-Lymphoma, Adult T-Cell
Mice
NF-kappa B
Signal Transduction
Transcriptional Activation

Chemicals

Gene Products, tax
NF-kappa B
tax protein, Human T-lymphotrophic virus 1
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 1

Word Cloud

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