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Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia

Freire Boullosa, Laurie; Savaliya, Payalben; Bonney, Stephanie; Orchard, Laurence; Wickenden, Hannah; Lee, Cindy; Smits, Evelien; Banham, Alison H.; Mills, Ken I.; Orchard, Kim; Guinn, Barbara

Authors

Laurie Freire Boullosa

Payalben Savaliya

Stephanie Bonney

Laurence Orchard

Hannah Wickenden

Cindy Lee

Evelien Smits

Alison H. Banham

Ken I. Mills

Kim Orchard

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is a rare heterogeneous disease characterized by a block in lymphoid differentiation and a rapid clonal expansion of immature, non-functioning B cells. Adult B-ALL patients have a poor prognosis with less than 50% chance of survival after five years and a high relapse rate after allogeneic haematopoietic stem cell transplantation. Novel treatment approaches are required to improve the outcome for patients and the identification of B-ALL specific antigens are essential for the development of targeted immunotherapeutic treatments.
We examined twelve potential target antigens for the immunotherapy of adult B-ALL. RT-PCR indicated that only survivin and WT1 were expressed in B-ALL patient samples (7/11 and 6/11, respectively) but not normal donor control samples (0/8). Real-time quantitative (RQ)-PCR showed that survivin was the only antigen whose transcript exhibited significantly higher expression in the B-ALL samples (n = 10) compared with healthy controls (n = 4)(p = 0.015). Immunolabelling detected SSX2, SSX2IP, survivin and WT1 protein expression in all ten B-ALL samples examined, but survivin was not detectable in healthy volunteer samples. To determine whether these findings were supported by the analyses of a larger cohort of patient samples, we performed metadata analysis on an already published microarray dataset. We found that only survivin was significantly over-expressed in B-ALL patients (n = 215) compared to healthy B-cell controls (n = 12)(p = 0.013).
We have shown that survivin is frequently transcribed and translated in adult B-ALL, but not healthy donor samples, suggesting this may be a promising target patient group for survivin-mediated immunotherapy.

Journal Article Type Article
Publication Date Dec 17, 2017
Journal OncoTarget
Print ISSN 1756-0500
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 9
Pages 3853-3866
Institution Citation Freire Boullosa, L., Savaliya, P., Bonney, S., Orchard, L., Wickenden, H., Lee, C., …Guinn, B. (2017). Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia. BMC research notes, 9, 3853-3866. https://doi.org/10.18632/oncotarget.23380
DOI https://doi.org/10.18632/oncotarget.23380
Keywords Acute lymphocytic leukemia; Antigen identification; Immunotherapy; Survivin; WT1
Publisher URL http://www.oncotarget.com
Additional Information Copyright: Boullosa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License
3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and
source are credited

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Copyright Statement
Copyright: Boullosa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License
3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and
source are credited





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