Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia
AuthorsBoullosa, Laura Freire
Bonney, Stephanie A.
Smits, Evelien L.J.
Banham, Alison H.
Mills, Ken I.
Orchard, Kim H.
AffiliationUniversity of Hull
University of Antwerp
University of Bedfordshire
University of Southampton
University of Oxford
Queens University Belfast
Subjectsacute lymphocytic leukemia
A900 Others in Medicine and Dentistry
MetadataShow full item record
AbstractB-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.
CitationBoullosa LF, Savaliya P, Bonney S, Orchard L, Wickenden H, Lee C, Smits E, Banham AH, Mills KI, Orchard K, Guinn BA (2018) 'Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia', Oncotarget, 9 (3), pp.3853-3866.
PubMed Central IDPMC5790505
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