Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia
| Autor: | Payalben Savaliya, Evelien Smits, Ken I. Mills, Alison H. Banham, Laurie Freire Boullosa, Cindy Lee, Stephanie Bonney, Barbara-Ann Guinn, Hannah Wickenden, Laurence Orchard, Kim Orchard |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Antigen identification
0301 basic medicine Oncology medicine.medical_specialty Microarray Survivin medicine.medical_treatment Acute lymphocytic leukemia survivin acute lymphocytic leukemia 03 medical and health sciences 0302 clinical medicine Antigen Internal medicine Medicine Biology business.industry antigen identification Immunotherapy medicine.disease WT1 Transplantation Haematopoiesis 030104 developmental biology 030220 oncology & carcinogenesis Human medicine immunotherapy Stem cell business Research Paper |
| Zdroj: | Oncotarget 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 2017, ' Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia ', Oncotarget, vol. 9, no. 3, pp. 3853-3866 . https://doi.org/10.18632/oncotarget.23380 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.23380 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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