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Koch A, Jeiler B, Roedig J, et al. Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines. Neoplasia. 2021;23(5):539-550doi: 10.1016/j.neo.2021.03.003.
Koch, A., Jeiler, B., Roedig, J., van Wijk, S. J. L., Dolgikh, N., & Fulda, S. (2021). Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines. Neoplasia (New York, N.Y.), 23(5), 539-550. https://doi.org/10.1016/j.neo.2021.03.003
Koch, Annkathrin, et al. "Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines." Neoplasia (New York, N.Y.) vol. 23,5 (2021): 539-550. doi: https://doi.org/10.1016/j.neo.2021.03.003
Koch A, Jeiler B, Roedig J, van Wijk SJL, Dolgikh N, Fulda S. Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines. Neoplasia. 2021 May;23(5):539-550. doi: 10.1016/j.neo.2021.03.003. Epub 2021 May 07. PMID: 33971465; PMCID: PMC8122156.
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Neoplasia. 2021 May;23(5):539-550. doi: 10.1016/j.neo.2021.03.003. Epub 2021 May 07.

Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines.

Neoplasia (New York, N.Y.)

Annkathrin Koch, Birte Jeiler, Jens Roedig, Sjoerd J L van Wijk, Nadezda Dolgikh, Simone Fulda

Affiliations

  1. Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
  2. Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Germany.
  3. Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Germany. Electronic address: [email protected].

PMID: 33971465 PMCID: PMC8122156 DOI: 10.1016/j.neo.2021.03.003

Abstract

Burkitt's lymphoma (BL) is a highly aggressive form of B-cell non-Hodgkin's lymphoma. The clinical outcome in children with BL has improved over the last years but the prognosis for adults is still poor, highlighting the need for novel treatment strategies. Here, we report that the combinational treatment with the Smac mimetic BV6 and TRAIL triggers necroptosis in BL when caspases are blocked by zVAD.fmk (TBZ treatment). The sensitivity of BL cells to TBZ correlates with MLKL expression. We demonstrate that necroptotic signaling critically depends on MLKL, since siRNA-induced knockdown and CRISPR/Cas9-mediated knockout of MLKL profoundly protect BL cells from TBZ-induced necroptosis. Conversely, MLKL overexpression in cell lines expressing low levels of MLKL leads to necroptosis induction, which can be rescued by pharmacological inhibitors, highlighting the important role of MLKL for necroptosis execution. Importantly, the methylation status analysis of the MLKL promoter reveals a correlation between methylation and MLKL expression. Thus, MLKL is epigenetically regulated in BL and might serve as a prognostic marker for treatment success of necroptosis-based therapies. These findings have crucial implications for the development of new treatment options for BL.

Copyright © 2021. Published by Elsevier Inc.

Keywords: Burkitt's lymphoma; MLKL; Necroptosis; Smac mimetics; TRAIL

References

  1. Nat Rev Mol Cell Biol. 2014 Feb;15(2):135-47 - PubMed
  2. Cell. 2011 Mar 4;144(5):646-74 - PubMed
  3. Mol Cancer Ther. 2015 Nov;14(11):2569-75 - PubMed
  4. Cancer Chemother Pharmacol. 2015 Apr;75(4):851-9 - PubMed
  5. Int J Cancer. 2020 Sep 1;147(5):1485-1498 - PubMed
  6. Cell Rep. 2017 May 30;19(9):1846-1857 - PubMed
  7. Front Pharmacol. 2018 Nov 06;9:1298 - PubMed
  8. Mol Cancer. 2019 May 23;18(1):100 - PubMed
  9. Mol Cell. 2014 Apr 10;54(1):133-146 - PubMed
  10. Oncogene. 2017 Mar;36(11):1487-1502 - PubMed
  11. PLoS One. 2020 Jan 8;15(1):e0227454 - PubMed
  12. Mol Cancer Ther. 2012 Jan;11(1):3-13 - PubMed
  13. Exp Biol Med (Maywood). 2016 Dec;241(18):2015-2022 - PubMed
  14. Cell Death Dis. 2014 Aug 21;5:e1384 - PubMed
  15. Cell Death Dis. 2018 Nov 1;9(11):1112 - PubMed
  16. J Mol Med (Berl). 2015 May;93(5):559-72 - PubMed
  17. Cancers (Basel). 2018 Dec 04;10(12): - PubMed
  18. Nature. 2015 Jan 15;517(7534):311-20 - PubMed
  19. Br J Surg. 1958 Nov;46(197):218-23 - PubMed
  20. Eur J Haematol. 2006 Jan;76(1):64-74 - PubMed
  21. Cancer Biol Ther. 2013 Nov;14(11):999-1004 - PubMed
  22. Cell Death Dis. 2020 Sep 11;11(9):744 - PubMed
  23. Transl Oncol. 2020 Feb;13(2):372-382 - PubMed
  24. Cell. 2009 Jun 12;137(6):1100-11 - PubMed
  25. Cell Death Dis. 2015 Sep 10;6:e1884 - PubMed
  26. Nat Immunol. 2000 Dec;1(6):489-95 - PubMed
  27. J Clin Oncol. 2014 Oct 1;32(28):3103-10 - PubMed
  28. BMC Cancer. 2009 Nov 06;9:392 - PubMed
  29. Clin Cancer Res. 2015 Nov 15;21(22):5030-6 - PubMed
  30. Int Rev Cell Mol Biol. 2017;328:253-275 - PubMed
  31. Biotechnol J. 2015 Apr;10(4):647-53 - PubMed
  32. Cell. 2012 Jul 20;150(2):339-50 - PubMed
  33. Br J Cancer. 2010 Jun 8;102(12):1707-16 - PubMed
  34. Cell Death Differ. 2016 May;23(5):748-56 - PubMed
  35. Cell Death Dis. 2014 May 01;5:e1201 - PubMed
  36. BMC Cancer. 2014 Feb 07;14:74 - PubMed
  37. Int J Oncol. 2013 Oct;43(4):1291-300 - PubMed
  38. Mol Cell. 2008 Jun 20;30(6):689-700 - PubMed
  39. Cell. 2012 Jan 20;148(1-2):213-27 - PubMed
  40. Cell. 2009 Jun 12;137(6):1112-23 - PubMed
  41. Cancer Res. 1997 Aug 15;57(16):3600-5 - PubMed
  42. Blood Adv. 2018 Dec 11;2(23):3516-3525 - PubMed
  43. Tumour Biol. 2015 Feb;36(2):769-77 - PubMed
  44. Blood. 2007 Apr 1;109(7):2773-80 - PubMed
  45. J Exp Med. 1998 Sep 7;188(5):919-30 - PubMed
  46. Science. 2009 Jul 17;325(5938):332-6 - PubMed
  47. Onco Targets Ther. 2018 Aug 22;11:5083-5092 - PubMed
  48. Int J Cancer. 2014 Nov 1;135(9):2223-31 - PubMed
  49. Breast Cancer Res Treat. 2013 Jan;137(2):359-71 - PubMed
  50. Cancer Res. 1997 Sep 1;57(17):3823-9 - PubMed
  51. Cancer Lett. 2016 Sep 28;380(1):31-8 - PubMed
  52. Nat Rev Drug Discov. 2012 Feb 01;11(2):109-24 - PubMed
  53. Semin Cell Dev Biol. 2015 Mar;39:132-8 - PubMed
  54. Cell Res. 2015 Jun;25(6):707-25 - PubMed
  55. BMC Cancer. 2019 May 24;19(1):496 - PubMed
  56. Insights Imaging. 2019 May 21;10(1):56 - PubMed

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