Skip to main content

Advertisement

SpringerLink
Log in

Expression and prognostic significance of livin/BIRC7 in childhood acute lymphoblastic leukemia

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Livin, a member of the inhibitor of apoptosis proteins has been considered to be a poor prognostic marker in malignancies. However, little is known about the clinical relevance of livin expression in childhood acute lymphoblastic leukemia (ALL). The aim of the present study was to assess the expression of livin on leukemic blasts of de novo childhood ALL and its relevance to clinical and hematological findings, and treatment outcome. The expression of livin was analyzed in 80 patients with newly diagnosed childhood ALL using quantitative reverse transcriptase-polymerase chain reaction. The results of the study revealed that the expression levels of livin were higher in patients with favorable prognostic factors. Furthermore, livin expression was associated with a favorable early response to chemotherapy (leukemic blast <25 % day 7 bone marrow response) (P = 0.001). Patients with high livin expression were associated with significantly higher CR rate (P = 0.02) and lower mortality rate (P = 0.05) than those with low livin expression. Kaplan–Meier curves demonstrated that high livin expression was associated with significantly longer DFS (P = 0.004) and overall survival (P = 0.02). Multivariate analysis demonstrated that livin expression was independent favorable prognostic factor for OS and DFS (P = 0.05 and P = 0.01, respectively). This study suggests that livin expression could be a novel prognostic marker in childhood ALL thus it could be incorporated into patient stratification and treatment protocols.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rana ZA, Rabbani MW, Sheikh MA, Khan AA. Outcome of childhood acute lymphoblastic leukemia after induction therapy 3 years experience at a single pediatric oncology centre. J Ayub Med Coll Abbottabad. 2009;21(4):150–3.

    PubMed  Google Scholar 

  2. Wang PP, Haines C. Childhood and adolescent leukemia in a North American population. Int J Epidemiol. 1995;24(6):1100–9.

    Article  CAS  PubMed  Google Scholar 

  3. Reed CJ. Apoptosis and cancer: strategies for integrating programmed cell death. Semin Hematol. 2000;37:9–16.

    Article  CAS  PubMed  Google Scholar 

  4. Schimmer AD, Hedley DW, Penn LZ, Minden MD. Receptor- and mitochondrial-mediated apoptosis in acute leukemia: a translational view. Blood. 2001;98(13):3541–53.

    Article  CAS  PubMed  Google Scholar 

  5. Nachmias B, Ashhab Y, Ben-Yehuda D. The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer. Semin Cancer Biol. 2004;14:231–43.

    Article  CAS  PubMed  Google Scholar 

  6. Choi J, Hwang YK, Sung KW, Lee SH, Yoo KH, Jung HL, Koo HH, Kim HJ, Kang HJ, Shin HY, Ahn HS. Expression of livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia. Blood. 2007;109(2):471–7.

    Article  CAS  PubMed  Google Scholar 

  7. Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM. ML-IAP. A novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol. 2000;10(21):1359–66.

    Article  CAS  PubMed  Google Scholar 

  8. Crnkovic-Mertens I, Muley T, Meister M, Hartenstein B, Semzow J, Butz K, Hoppe-Seyler F. The anti-apoptotic livin gene is an important determinant for the apoptotic resistance of non-small cell lung cancer cells. Lung Cancer. 2006;54:135–42.

    Article  PubMed  Google Scholar 

  9. Nachmias B, Ashhab Y, Bucholtz V, Drize O, Kadouri L, Lotem M, Peretz T, Mandelboim O, Ben-Yehuda D. Caspase mediated cleavage converts livin from an antiapoptotic to a proapoptotic factor: implications for drug-resistant melanoma. Cancer Res. 2003;63:6340–9.

    CAS  PubMed  Google Scholar 

  10. Ma L, Huang Y, Song Z, Feng S, Tian X, Du W, Qiu X, Heese K, Wu M. Livin promotes Smac/DIABLO degradation by ubiquitin-proteasome pathway. Cell Death Differ. 2006;13(12):2079–88.

    Article  CAS  PubMed  Google Scholar 

  11. Kim DK, Alvarado CS, Abramowsky CR, Gu L, Zhou M, Soe MM, Sullivan K, George B, Schemankewitz E, Findley HW. Expression of inhibitor-of-apoptosis protein (IAP) livin by neuroblastoma cells: correlation with prognostic factors and outcome. Pediatr Dev Pathol. 2005;8(6):621–9.

    Article  CAS  PubMed  Google Scholar 

  12. Holleman A, Den Boer ML, Kazemier KM, Janka-Schaub GE, Pieters R. Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia. Blood. 2003;102:4541–6.

    Article  CAS  PubMed  Google Scholar 

  13. Harms DO, Janka-Schaub GE. Cooperative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92. Leukemia. 2000;14:2234–9.

    Article  CAS  PubMed  Google Scholar 

  14. Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML, Chan GC, Pui CH, Grosveld G, Downing JR. TEL/AML1 fusion resulting from a cryptic t (12; 21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia. 1995;9:1985–9.

    CAS  PubMed  Google Scholar 

  15. Kasof GM, Gomes BC. Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem. 2001;276:3238–46.

    Article  CAS  PubMed  Google Scholar 

  16. Deveraux QL, Reed JC. IAP family proteins—suppressors of apoptosis. Genes Dev. 1999;13:239–52.

    Article  CAS  PubMed  Google Scholar 

  17. Tamm I, Kornblau SM, Segall H, et al. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000;6:1796–803.

    CAS  PubMed  Google Scholar 

  18. Yan B. Research progress on Livin protein: an inhibitor of apoptosis. Mol Cell Biochem. 2011;357(1–2):39–45.

    Article  CAS  PubMed  Google Scholar 

  19. Yang YL, Lin SR, Chen JS, Lin SW, Yu SL, Chen HY, Yen CT, Lin CY, Lin JF, Lin KH, Jou ST, Hu CY, Chang SK, Lu MY, Chang HH, Chang WH, Lin KS, Lin DT. Expression and prognostic significance of the apoptotic genes BCL2L13, Livin, and CASP8AP2 in childhood acute lymphoblastic leukemia. Leuk Res. 2010;34(1):18–23.

    Article  CAS  PubMed  Google Scholar 

  20. El-Mesallamy HO, Hegab HM, Kamal AM. Expression of inhibitor of apoptosis protein (IAP) livin/BIRC7 in acute leukemia in adults: correlation with prognostic factors and outcome. Leuk Res. 2011;35(12):1616–22.

    Article  CAS  PubMed  Google Scholar 

  21. Flotho C, Coustan-Smith E, Pei D, Cheng C, Song G, Pui C-H, et al. A set of genes that regulate cell proliferation predicts treatment outcome in childhood acute lymphoblastic leukemia. Blood. 2007;110(4):1271–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Wuchter C, Richter S, Oltersdorf D, Karawajew L, Ludwig W, Tamm I. Differences in the expression pattern of apoptosis-related molecules between child-hood and adult de novo acute myeloid leukemia. Haematologica. 2004;89(3):363–4.

    CAS  PubMed  Google Scholar 

  23. Coustan-Smith E, Kitanaka A, Pui C. Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia. Blood. 1996;87:1140–6.

    CAS  PubMed  Google Scholar 

  24. Campos L, Sabido O, Sebban C, Charrin C, Bertheas M, Fière D, et al. Expression of BCL-2 proto-oncogene in adult acute lymphoblastic leukemia. Leukemia. 1996;10(3):434–8.

    CAS  PubMed  Google Scholar 

  25. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

    Article  CAS  PubMed  Google Scholar 

  26. Dohner K, Dohner H. Molecular characterization of acute myeloid leukemia. Haematologica. 2008;93(7):976–82.

    Article  PubMed  Google Scholar 

  27. Kaspers GJ, Veerman AJ, Pieters R, et al. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood. 1997;90:2723–9.

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest

All authors have no conflict of interest to report.

Author information

Authors and Affiliations

  1. Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura, Egypt

    Lamia Ibrahim & Doaa Aladle

  2. Pediatric Department, Mansoura Faculty of Medicine, Mansoura, Egypt

    Ahmed Mansour, Ayman Hammad, Angi Adel Al Wakeel & Suzy A Abd El-Hameed

Authors
  1. Lamia Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Doaa Aladle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed Mansour
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayman Hammad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Angi Adel Al Wakeel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Suzy A Abd El-Hameed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lamia Ibrahim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ibrahim, L., Aladle, D., Mansour, A. et al. Expression and prognostic significance of livin/BIRC7 in childhood acute lymphoblastic leukemia. Med Oncol 31, 941 (2014). https://doi.org/10.1007/s12032-014-0941-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0941-4

Keywords

Search

Navigation