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

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

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.

Citation

Boullosa, L. F., Savaliya, P., Bonney, S., Orchard, L., Wickenden, H., Lee, C., Smits, E., Banham, A. H., Mills, K. I., Orchard, K., & Guinn, B. A. (2018). Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia. Oncotarget, 9(3), 3853-3866. https://doi.org/10.18632/oncotarget.23380

• Journal Article Type: Article
• Acceptance Date: Nov 26, 2017
• Online Publication Date: Dec 17, 2017
• Publication Date: Jan 1, 2018
• Deposit Date: Sep 3, 2019
• Publicly Available Date: Sep 3, 2019
• Journal: Oncotarget
• Print ISSN: 1949-2553
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 3
• Pages: 3853-3866
• DOI: https://doi.org/10.18632/oncotarget.23380
• Keywords: Acute lymphocytic leukemia; Antigen identification; Immunotherapy; Survivin; WT1
• Public URL: https://hull-repository.worktribe.com/output/588305
• 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
• Contract Date: Sep 3, 2019