Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

T and B leukemic cell lines exhibit different requirements for cell death: correlation between caspase activation, DFF40/DFF45 expression, DNA fragmentation and apoptosis in T cell lines but not in Burkitt's lymphoma

Leukemia volume 16, pages 700–707 (2002)Cite this article

Abstract

The execution phase of apoptosis occurs through the activation and function of caspases which cleave key substrates that orchestrate the death process. Here, we have compared the sensitivity of various T and B cell lines to death receptor or staurosporine-induced apoptosis. First, we found a lack of correlation between death receptor expression and sensitivity to Fas or Trail. By contrast, a correlation between caspase activation, DNA fragmentation and cell death in T cell lines was evidenced. Among T cells, CEM underwent apoptosis in response to CH11 but were resistant to Trail in agreement with the absence of Trail receptors (DR4 and DR5) on their surface. The B cell line SKW 6.4 was sensitive to CH11 and staurosporine but resistant to Trail. As B cell lines expressed significant levels of DR4 and DR5, resistance to Trail in SKW 6.4 is likely due to the expression of the decoy receptor DcR1. Burkitt's lymphoma such as RPMI 8866 and Raji did not exhibit DNA fragmentation in response to CH11, Trail or staurosporine but showed long-term caspase-dependent loss of viability upon effector treatment. The B cell lines used in this study express very weak or undetectable levels of DFF40 and relatively high levels of DFF45. Interestingly, cytosolic extracts from RPMI 88.66 but not other B lymphoma exhibit altered levels of cytochrome c-dependent caspase activation. Taken together, our results show that: (1) death receptor expression does not correlate with sensitivity to apoptosis; (2) the very low ratio of DFF40 vs DFF45 is unlikely to explain by itself the lack of DNA fragmentation observed in certain B cell lines; and (3) a defective cytochrome c-dependent caspase activation might account at least in part for the insensitivity of certain Burkitt's lymphoma (RPMI 88.66) to apoptosis. Thus it seems that resistance of Burkitt's lymphoma to apoptosis is not governed by a general mechanism, but is rather multifactorial and differs from one cell line to another.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Thompson CB . Apoptosis in the pathogenesis and treatment of disease Science 1995 267: 1456–1462

    Article  CAS  PubMed  Google Scholar 

  2. Nagata S . Human autoimmune lymphoproliferative syndrome, a defect in the apoptosis-inducing Fas receptor: a lesson from the mouse model J Hum Genet 1998 43: 2–8

    Article  CAS  PubMed  Google Scholar 

  3. Vaux DL, Cory S, Adams JM . Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells Nature 1988 335: 440–442

    Article  CAS  PubMed  Google Scholar 

  4. Nunez G, London L, Hockenbery D, Alexander M, McKearn JP, Korsmeyer SJ . Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines J Immunol 1990 144: 3602–3610

    CAS  PubMed  Google Scholar 

  5. Campana D, Coustan-Smith E, Manabe A, Buschle M, Raimondi SC, Behm R, Ashmun FG, Arico M, Biondi A, Pui CH . Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2 protein Blood 1993 81: 1025–1031

    CAS  PubMed  Google Scholar 

  6. Ashkenazi A, Dixit VM . Death receptors: signaling and modulation Science 1998 281: 1305–1308

    Article  CAS  PubMed  Google Scholar 

  7. Peter ME, Krammer PH . Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis Curr Opin Immunol 1998 10: 545–551

    Article  CAS  PubMed  Google Scholar 

  8. Chinnaiyan AM, Tepper CG, Seldin MF, O'Rourke K, Kischkel FC, Hellbardt S, Krammer PH, Peter ME, Dixit VM . FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis J Biol Chem 1996 271: 4961–4965

    Article  CAS  PubMed  Google Scholar 

  9. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM . FADD, a death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis Cell 1995 81: 502–512

    Article  Google Scholar 

  10. Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevehenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM . FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex Cell 1996 85: 817–827

    Article  CAS  PubMed  Google Scholar 

  11. Muzio M, Stockwell BR, Stennicke HR, Salvesen GS, Dixit VM . An induced proximity model for caspase-8 activation J Biol Chem 1998 273: 2926–2930

    Article  CAS  PubMed  Google Scholar 

  12. Hasegawa J, Kamada S, Kamiike W, Shimizu S, Imazu T, Matsuda H, Tsujimoto M . Involvement of CPP32/YAMA (-like) proteases in Fas-mediated apoptosis Cancer Res 1996 56: 1713–1718

    CAS  PubMed  Google Scholar 

  13. Enari M, Talanian RV, Wong WW, Nagata S . Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis Nature 1996 380: 723–726

    Article  CAS  PubMed  Google Scholar 

  14. Dubrez L, Savoy I, Hamman A, Solary E . Pivotal role of a DEVD-sensitive step in etoposide-induced and Fas-mediated apoptotic pathways EMBO J 1996 15: 5504–5512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Juan TS, McNiece IK, Argento JM, Jenkins NA, Gilbert DJ, Copeland NG, Fletcher FA . Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3 Genomics 1997 40: 86–97

    Article  CAS  PubMed  Google Scholar 

  16. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S . A caspase activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD Nature 1997 391: 43–50

    Article  Google Scholar 

  17. Sakahira H, Enari M, Nagata S . Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis Nature 1998 391: 96–99

    Article  CAS  PubMed  Google Scholar 

  18. Li LY, Luo X, Wang X . Endonuclease G is an apoptotic DNase when released from mitochondria Nature 2001 412: 95–99

    Article  CAS  PubMed  Google Scholar 

  19. Mari B, Checler F, Ponzio G, Peyron JF, Manie S, Farahifar D, Rossi B, Auberger P . Jurkat T cells express a functional neutral endopeptidase activity (CALLA) involved in T cell activation EMBO J 1992 11: 3875–3885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bourget I, Di Berardino W, Breittmayer JP, Grenier-Brossette N, Plana-Prades M, Bonnefoy JY, Cousin JL . CD20 monoclonal antibodies stimulate extracellular cleavage of the low affinity receptor for IgE (Fc epsilon RII/CD23) in Epstein-Barr-transformed B cells J Biol Chem 1994 269: 6927–6930

    CAS  PubMed  Google Scholar 

  21. Munoz O, Brignone C, Grenier-Brossette N, Bonnefoy JY, Cousin JL . Binding of anti-CD23 monoclonal antibody to the leucine zipper motif of FcepsilonRII/CD23 on B cell membrane promotes its proteolytic cleavage. Evidence for an effect on the oligomer/monomer equilibrium J Biol Chem 1998 273: 31795–31800

    Article  CAS  PubMed  Google Scholar 

  22. Ricci JE, Maulon L, Luciano F, Guerin S, Livolsi A, Mari B, Breittmayer JP, Peyron JF, Auberger P . Cleavage and relocation of tyrosine kinase P59FYN during Fas-mediated apoptosis in T lymphocytes Oncogene 1999 18: 3963–3969

    Article  CAS  PubMed  Google Scholar 

  23. Bertolotto C, Ricci JE, Luciano F, Mari B, Chambard JC, Auberger P . Cleavage of the serum response factor during death receptor-induced apoptosis results in an inhibition of the c-FOS promoter transcriptional activity J Biol Chem 2000 275: 12941–12947

    Article  CAS  PubMed  Google Scholar 

  24. Mari B, Guerin S, Maulon L, Belhacene N, Farahi Far D, Imbert V, Rossi B, Peyron JF, Auberger P . Endopeptidase 24.11 (CD10/NEP) is required for phorbol ester-induced growth arrest in Jurkat T cells FASEB J 1997 11: 869–879

    Article  CAS  PubMed  Google Scholar 

  25. Guerin S, Mari B, Fernandez E, Belhacene N, Toribio ML, Auberger P . CD10 is expressed on human thymic epithelial cell lines and modulates thymopentin-induced cell proliferation FASEB J 1997 11: 1003–1011

    Article  CAS  PubMed  Google Scholar 

  26. Pages G, Guerin S, Grall D, Bonino F, Smith A, Anjuere F, Auberger P, Pouyssegur J . Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice Science 1999 286: 1374–1377

    Article  CAS  PubMed  Google Scholar 

  27. Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner EB, Mueller-Dieckmann C, Farahifar D, Rossi B, Auberger P, Baeuerle PA, Peyron JF . Tyrosine phosphorylation of 1 kappa B-alpha activates NF-kappa B without proteolytic degradation of 1 kappa B-alpha Cell 1996 86: 787–798

    Article  CAS  PubMed  Google Scholar 

  28. Maulon L, Guerin S, Ricci JE, Breittmayer DF, Auberger P . T-cell receptor signaling pathway exerts a negative control on thrombin-mediated increase in [Ca2+]i and p38 MAPK activation in Jurkat T cells: implication of the tyrosine kinase p56Lck Blood 1998 91: 4232–4241

    CAS  PubMed  Google Scholar 

  29. Cursio R, Gugenheim J, Ricci JE, Crenesse D, Rostagno P, Maulon L, Saint-Paul MC, Ferrua B, Auberger P . A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis FASEB J 1999 13: 253–261

    Article  CAS  PubMed  Google Scholar 

  30. Wolf BW, Schuler M, Li W, Eggers-Sedlet B, Lee W, Tailor P, Fitzgerald P, Mills GB, Green DG . Defectice cytochrome C-dependent caspase activation in ovarian cancer cell lines due to diminished or absent APAF-1 activity J Biol Chem 2001 276: 34244–34251

    Article  CAS  PubMed  Google Scholar 

  31. Shain KH, Landwoski TH, Buyuksal I, Cantor AB, Dalton WS . Clonal variability in CD9 expression is the major determinant in Fas-mediated, but not chemotherapy-mediated apoptosis in the RPMI 8226 multiple myeloma cell line Leukemia 2000 14: 830–840

    Article  CAS  PubMed  Google Scholar 

  32. Tepper CG, Seldin MF . Modulation of caspase-8 and FLICE-inhibitory protein expression as a potential mechanism of Epstein–Barr virus tumorigenesis in Burkitt's lymphoma Blood 1999 94: 1727–1737

    CAS  PubMed  Google Scholar 

  33. Irissari M, Plumas J, Bonnefoix T, Jacob MC, Roucard C, Pasquier MA, Sotto JJ, Lajmanovich A . Resistance to CD95-mediated apoptosis through constitutive c-FLIP expression in a non-hodgkin's lymphoma B cell line Leukemia 2000 14: 2149–2158

    Article  Google Scholar 

  34. Zermati Y, Garrido C, Amsellem S, Ffishelson S, Bouscary D, Valensi F, Varet B, Solary E, Hermine O . Caspase activation is required for terminal erythroid differienciation J Exp Med 2001 193: 247–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. De Maria R, Zeuner A, Eramo A, Domenichelli C, Bonci D, Grignani F, Srinivasula SM, Alnemri ES, Testa U, Peschle C . Negative regulation of erythropoiesis by caspase mediated cleavage of GATA-1 Nature 1999 401: 433–435–436

    Article  Google Scholar 

  36. Blagosklonny MV . Cell death beyond apoptosis Leukemia 2000 14: 1502–1508

    Article  CAS  PubMed  Google Scholar 

  37. Sakahira H, Enari M, Ohsawa Y, Uchiyama Y, Nagata S . Apoptotic nuclear morphological change without DNA fragmentation Curr Biol 1999 9: 543–546

    Article  CAS  PubMed  Google Scholar 

  38. Kawabata Y, Hirokawa M, Kitabayashi A, Horiuchi T, Kuroki J, Miura AB . Defective apoptotic signal transduction pathway downstream of caspase-3 in human B-lymphoma cells: a novel mechanism of nuclear apoptosis resistance Blood 1999 94: 3523–3530

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by INSERM, the Fondation de France and the Ligue Nationale Contre le Cancer (Equipe labellisée).

Author information

Authors and Affiliations

  1. INSERM U 526, Activation des cellules Hématopoïétiques, Equipe labellisée par la Ligue Nationale contre le Cancer, IFR 50, Faculté de Médecine, Nice, France

    F Luciano, J-E Ricci, M Herrant, C Bertolotto, B Mari & P Auberger

  2. INSERM U343, IFR50, Hôpital de l'Archet, Nice, France

    J-L Cousin

Authors
  1. F Luciano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J-E Ricci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Herrant
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Bertolotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B Mari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J-L Cousin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Auberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luciano, F., Ricci, JE., Herrant, M. et al. T and B leukemic cell lines exhibit different requirements for cell death: correlation between caspase activation, DFF40/DFF45 expression, DNA fragmentation and apoptosis in T cell lines but not in Burkitt's lymphoma. Leukemia 16, 700–707 (2002). https://doi.org/10.1038/sj.leu.2402401

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402401

Keywords

This article is cited by

Search

Advanced search

Quick links