Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia

Anja Troeger, Meinolf Siepermann, Gabriele Escherich, Roland Meisel, Reinhardt Willers, Sonja Gudowius, Thomas Moritz, Hans Juergen Laws, Helmut Hanenberg, Ulrich Goebel, Gritta E. Janka-Schaub, Csaba Mahotka, Dagmar Dilloo

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background and Objectives: Impaired apoptosis, mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin, is thought to contribute to leukemic cell survival. In contrast to low expression of survivin in normal differentiated adult tissues, very high levels of survivin have been described in a number of different tumors. Overexpression of survivin was found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. To date, however, there is no information available on the prognostic role of survivin in pediatric precursor B-cell acute lymphocytic leukemia (BCP-ALL), the most frequent malignancy in childhood. Design and Methods: In a retrospective study including 66 pediatric patients we analyzed the impact of survivin protein levels on outcome in BCP-ALL. Results: Survivin overexpression, with an up to ten-fold increase of the normal level, was detected in 65% of the leukemic samples in contrast to negligible expression in non-malignant hematopoietic cells. Despite considerable variety of expression levels in ALL cells, there was no association of survivin levels with established risk factors. However, patients suffering relapse of disease or death had significantly higher survivin expression than those with a favorable outcome. Overexpression of survivin is a significant prognostic marker for 3 year relapse free, event-free and overall survival, again independent of the established prognostic factors in ALL, such as age and leukocyte count at diagnosis as assessed in multivariate analysis. Interpretation and Conclusions: Overexpression of survivin in BCP-ALL identifies patients with a high risk of early relapse. Upon confirmation in a prospective analysis, survivin expression may, in the future, serve to further refine treatment stratification with intensification of therapy in those patients prone to relapse.

Original languageEnglish (US)
Pages (from-to)1043-1050
Number of pages8
JournalHaematologica
Volume92
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Recurrence
B-Cell Leukemia
Inhibitor of Apoptosis Proteins
Neoplasms
B-Lymphoid Precursor Cells
Hematologic Neoplasms
Leukocyte Count
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Cell Survival
Multivariate Analysis
Retrospective Studies
Apoptosis
Therapeutics
Proteins

Keywords

  • Apoptosis
  • BCP-ALL
  • Prognosis
  • Survivin

ASJC Scopus subject areas

  • Hematology

Cite this

Troeger, A., Siepermann, M., Escherich, G., Meisel, R., Willers, R., Gudowius, S., ... Dilloo, D. (2007). Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia. Haematologica, 92(8), 1043-1050. https://doi.org/10.3324/haematol.10675

Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia. / Troeger, Anja; Siepermann, Meinolf; Escherich, Gabriele; Meisel, Roland; Willers, Reinhardt; Gudowius, Sonja; Moritz, Thomas; Laws, Hans Juergen; Hanenberg, Helmut; Goebel, Ulrich; Janka-Schaub, Gritta E.; Mahotka, Csaba; Dilloo, Dagmar.

In: Haematologica, Vol. 92, No. 8, 08.2007, p. 1043-1050.

Research output: Contribution to journalArticle

Troeger, A, Siepermann, M, Escherich, G, Meisel, R, Willers, R, Gudowius, S, Moritz, T, Laws, HJ, Hanenberg, H, Goebel, U, Janka-Schaub, GE, Mahotka, C & Dilloo, D 2007, 'Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia', Haematologica, vol. 92, no. 8, pp. 1043-1050. https://doi.org/10.3324/haematol.10675
Troeger A, Siepermann M, Escherich G, Meisel R, Willers R, Gudowius S et al. Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia. Haematologica. 2007 Aug;92(8):1043-1050. https://doi.org/10.3324/haematol.10675
Troeger, Anja ; Siepermann, Meinolf ; Escherich, Gabriele ; Meisel, Roland ; Willers, Reinhardt ; Gudowius, Sonja ; Moritz, Thomas ; Laws, Hans Juergen ; Hanenberg, Helmut ; Goebel, Ulrich ; Janka-Schaub, Gritta E. ; Mahotka, Csaba ; Dilloo, Dagmar. / Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia. In: Haematologica. 2007 ; Vol. 92, No. 8. pp. 1043-1050.
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AU - Willers, Reinhardt

AU - Gudowius, Sonja

AU - Moritz, Thomas

AU - Laws, Hans Juergen

AU - Hanenberg, Helmut

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