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.

  • Letter to the Editor
  • Published:

Caspase-independent type III PCD: a new means to modulate cell death in chronic lymphocytic leukemia

Leukemia volume 23, pages 974–977 (2009)Cite this article

Chronic lymphocytic leukemia (CLL) represents a perfect example of a human malignancy caused by an imbalance between proliferation and programmed cell death (PCD).1 This disease is characterized by the accumulation of monoclonal B cells (CD20+, CD5+ and CD23+) in the peripheral blood, bone marrow and secondary lymphoid organs.2 CLL was initially considered as a disease deriving from an inherent defect in PCD. However, more recent studies suggest that accumulation of CLL cells could be a consequence of excessive proliferation, defective PCD or deregulation in proliferation/PCD ratios.1 The unraveling of the molecular mechanisms controlling PCD in CLL will therefore provide (i) a better understanding of the disease and (ii) a rationale for the development of specific drugs that modulate pathological PCD.

Although PCD has traditionally been equated with caspase activation and with apoptosis, it is now accepted that non-apoptotic, non-caspase-dependent forms of PCD exist in immune system cells.3 Indeed, the cell can use three mechanisms/pathways to accomplish its proper demise. These pathways are defined as type I, type II or type III PCD.4 Type I PCD, or classical apoptosis, is caspase-dependent. Type II PCD is characterized by the appearance of autophagic vacuoles and seems not to be related to caspases. Type III PCD is caspase-independent and occurs without pronounced nuclear chromatin condensation. The molecular pathways incriminated in this last type of PCD are poorly understood.

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

References

  1. Chiorazzi N . Cell proliferation and death: forgotten features of chronic lymphocytic leukemia B cells. Best Pract Res Clin Haematol 2007; 20: 399–413.

    Article  CAS  Google Scholar 

  2. Dighiero G, Hamblin TJ . Chronic lymphocytic leukaemia. Lancet 2008; 371: 1017–1029.

    Article  CAS  Google Scholar 

  3. Jaattela M, Tschopp J . Caspase-independent cell death in T lymphocytes. Nat Immunol 2003; 4: 416–423.

    Article  Google Scholar 

  4. Gozuacik D, Kimchi A . Autophagy and cell death. Curr Top Dev Biol 2007; 78: 217–245.

    Article  CAS  Google Scholar 

  5. Bras M, Yuste VJ, Roue G, Barbier S, Sancho P, Virely C et al. drp1 mediates caspase-independent type III cell death in normal and leukemic cells. Mol Cell Biol 2007; 27: 7073–7088.

    Article  CAS  Google Scholar 

  6. Lindberg FP, Gresham HD, Schwarz E, Brown EJ . Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane-spanning domains implicated in alpha v beta 3-dependent ligand binding. J Cell Biol 1993; 123: 485–496.

    Article  CAS  Google Scholar 

  7. Roue G, Bitton N, Yuste VJ, Montange T, Rubio M, Dessauge F et al. Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS production in the absence of cytochrome c and AIF release. Biochimie 2003; 85: 741–746.

    Article  CAS  Google Scholar 

  8. Grabs D, Slepnev VI, Songyang Z, David C, Lynch M, Cantley LC et al. The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence. J Biol Chem 1997; 272: 13419–13425.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M Segade for proofreading and C Virely, P Sancho and VJ Yuste for data. This work was supported by the Fondation de France-Comité Leucémie, Ligue Contre le Cancer, and the Association pour la Recherche sur le Cancer (ARC; contract no. 4043 to SAS), as well as a grant from the Canadian Institute for Health and Research (MOP-53152 to MS). SB was supported by a PhD fellowship from MENRT.

Author information

Authors and Affiliations

  1. INSERM, U872, Mort Cellulaire Programmée et Physiopathologie des Cellules Tumorales, Equipe 19, Centre de Recherche des Cordeliers, Paris, France

    H Merle-Béral, S Barbier & S A Susin

  2. Université Pierre et Marie Curie-Paris 6, UMRS 872, Paris, France

    H Merle-Béral, S Barbier & S A Susin

  3. Université Paris Descartes, UMRS 872, Paris, France

    H Merle-Béral, S Barbier & S A Susin

  4. AP-HP, Groupe Hospitalier Pitie-Salpêtrière, Service d’Hématologie Biologique, Paris, France

    H Merle-Béral

  5. CNRS, URA 1961, Institut Pasteur, Paris, France

    S Barbier, G Roué, M Bras & S A Susin

  6. Centre de Recherche du CHUM, Hôpital Notre-Dame, Laboratoire d’Immunorégulation, Montréal, Canada

    M Sarfati

Authors
  1. H Merle-Béral
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Barbier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Roué
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Bras
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Sarfati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S A Susin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S A Susin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Merle-Béral, H., Barbier, S., Roué, G. et al. Caspase-independent type III PCD: a new means to modulate cell death in chronic lymphocytic leukemia. Leukemia 23, 974–977 (2009). https://doi.org/10.1038/leu.2008.321

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2008.321

This article is cited by

  • CD47

    • William Frazier
    • Jeffrey Isenberg
    • David Roberts

    AfCS-Nature Molecule Pages (2010)

Search

Advanced search

Quick links