European Journal of Cancer
Volume 46, Issue 4 , Pages 800-810, March 2010

Expression and prognostic significance of the inhibitor of apoptosis protein (IAP) family and its antagonists in chronic lymphocytic leukaemia☆

  • Olga Grzybowska-Izydorczyk

      Affiliations

    • Department of Experimental Haematology, Medical University of Lodz, Copernicus Memorial Hospital, Ciolkowskiego 2, 93-510 Lodz, Poland
    • ,
  • Barbara Cebula

      Affiliations

    • Department of Experimental Haematology, Medical University of Lodz, Copernicus Memorial Hospital, Ciolkowskiego 2, 93-510 Lodz, Poland
    • ,
  • Tadeusz Robak

      Affiliations

    • Department of Haematology, Medical University of Lodz, Lodz, Poland
    • ,
  • Piotr Smolewski

      Affiliations

    • Department of Experimental Haematology, Medical University of Lodz, Copernicus Memorial Hospital, Ciolkowskiego 2, 93-510 Lodz, Poland
    • Corresponding Author InformationCorresponding author: Tel.: +48 42 689 51 91; fax: +48 42 689 51 92.

Received 20 May 2009; received in revised form 22 September 2009; accepted 25 November 2009. published online 04 January 2010.

Abstract 

Impaired apoptosis is still considered to be an important event in the development and progression of chronic lymphocytic leukaemia (CLL). However, mechanisms of this defect have not been fully elucidated. In this study, expression of inhibitor of apoptosis proteins, IAPs (cIAP1, cIAP2, XIAP and survivin), and their antagonists (Smac/DIABLO and HtrA2/Omi) was comprehensively analysed in 100 untreated CLL patients, using flow cytometry and Western blot techniques.

Expression of anti-apoptotic cIAP1 and cIAP2 in leukaemic cells was significantly higher than in non-tumour lymphocytes (p=0.000001 and p=0.014, respectively), whereas the IAP-antagonist, Smac/DIABLO, was decreased in CLL (p=0.010). Higher expression of all analysed IAPs (cIAP1, p=0.002; cIAP2, p=0.026; XIAP, p=0.002; survivin, p=0.00006) and lower levels of Smac/DIABLO (p=0.006) were found in patients with progressive disease, compared to those with stable CLL. High baseline expression of cIAP1 and survivin correlated with worse response to treatment. Co-expression of these proteins was associated with shorter overall survival of CLL patients (p=0.005).

In conclusion, CLL cells show the apoptosis-resistant profile of IAPs/IAP-antagonist expression. Upregulation of IAPs is associated with a progressive course of the disease. Co-expression of cIAP1 and survivin seems to be an unfavourable prognostic factor in CLL patients. Further studies with longer follow up are warranted to confirm and expand these findings.

Keywords: Chronic lymphocytic leukaemia, Apoptosis, Inhibitor of apoptosis protein family, Prognosis

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☆ The data were presented at an oral session at the 50th Annual Meeting of the American Society of Haematology, San Francisco, December 6–9, 2008.

PII: S0959-8049(09)00877-6

doi:10.1016/j.ejca.2009.11.023

European Journal of Cancer
Volume 46, Issue 4 , Pages 800-810, March 2010

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