Oncotarget

Research Papers:

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

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

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Oncotarget. 2018; 9:3853-3866. https://doi.org/10.18632/oncotarget.23380

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Abstract

Laurie Freire Boullosa1,2,*, Payalben Savaliya3,*, Stephanie Bonney4, Laurence Orchard4, Hannah Wickenden4, Cindy Lee4,5, Evelien Smits2, Alison H. Banham6, Ken I. Mills7, Kim Orchard5 and Barbara-Ann Guinn1,3,4

1School of Life Sciences – Biomedical Science Subject Group, University of Hull, Hull, HU7 6RX, UK

2Centre for Oncological Research, University of Antwerp, 2610 Antwerp, Belgium

3Department of Life Sciences, University of Bedfordshire, Park Square, Luton, LU1 3JU, UK

4Cancer Sciences Unit, Somers Cancer Sciences Building, University of Southampton, Southampton SO16 6YD, UK

5Department of Haematology, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, UK

6Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK

7Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast BT9 7AE, UK

*These authors contributed equally to the work

Correspondence to:

Barbara-Ann Guinn, email: [email protected]

Keywords: acute lymphocytic leukemia; antigen identification; immunotherapy; survivin; WT1

Received: September 01, 2017     Accepted: November 26, 2017     Published: December 17, 2017

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.


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