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.
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.
Authors: Asmaa M Esh; Maha Atfy; Nashwa A Azizi; Mohamed M El Naggar; Ebtesam E Khalil; Layla Sherief Journal: Indian J Hematol Blood Transfus Date: 2011-02-12 Impact factor: 0.900
Authors: Alisa B Lee-Sherick; Rachel M A Linger; Lia Gore; Amy K Keating; Douglas K Graham Journal: Br J Haematol Date: 2010-08-31 Impact factor: 6.998
Authors: Fiona M Foster; Thomas W Owens; Jolanta Tanianis-Hughes; Robert B Clarke; Keith Brennan; Nigel J Bundred; Charles H Streuli Journal: Breast Cancer Res Date: 2009-06-29 Impact factor: 6.466
Authors: E Sugantha Priya; K Selvakumar; S Bavithra; P Elumalai; R Arunkumar; P Raja Singh; A Brindha Mercy; J Arunakaran Journal: Neurol Sci Date: 2013-06-16 Impact factor: 3.307