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

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

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.

Acute lymphocytic leukemia, Antigen identification, Immunotherapy, Survivin, WT1
1949-2553
3853-3866
Boullosa, Laurie Freire
d84e5216-bf7b-42b4-b69a-f78a1d1a941c
Savaliya, Payalben
e4614224-4a07-4960-894b-ceb00bba05ea
Bonney, Stephanie
a27927d4-b76c-4ab9-b9fb-b60339619033
Orchard, Laurence
1020d548-60bb-4227-be10-fdb7ae3c6e12
Wickenden, Hannah
0d449499-70f2-4fe9-8665-ecb7b00a3d9f
Lee, Cindy
9f619f94-1da0-4a60-94a4-0d634e6a8850
Smits, Evelien
516028c8-534a-4498-bf94-97a95af08c59
Banham, Alison H.
f6182d3c-803c-452a-82b0-002a2ad0e8e3
Mills, Ken I.
33f95cd3-8ca0-4b21-bfbf-52e759488670
Orchard, Kim
794654ab-d6cc-488a-ac11-c9217433c7a2
Guinn, Barbara Ann
48baa19f-4b9e-4fbd-9fc9-8071e090b854
Boullosa, Laurie Freire
d84e5216-bf7b-42b4-b69a-f78a1d1a941c
Savaliya, Payalben
e4614224-4a07-4960-894b-ceb00bba05ea
Bonney, Stephanie
a27927d4-b76c-4ab9-b9fb-b60339619033
Orchard, Laurence
1020d548-60bb-4227-be10-fdb7ae3c6e12
Wickenden, Hannah
0d449499-70f2-4fe9-8665-ecb7b00a3d9f
Lee, Cindy
9f619f94-1da0-4a60-94a4-0d634e6a8850
Smits, Evelien
516028c8-534a-4498-bf94-97a95af08c59
Banham, Alison H.
f6182d3c-803c-452a-82b0-002a2ad0e8e3
Mills, Ken I.
33f95cd3-8ca0-4b21-bfbf-52e759488670
Orchard, Kim
794654ab-d6cc-488a-ac11-c9217433c7a2
Guinn, Barbara Ann
48baa19f-4b9e-4fbd-9fc9-8071e090b854

Boullosa, Laurie Freire, Savaliya, Payalben, Bonney, Stephanie, Orchard, Laurence, Wickenden, Hannah, Lee, Cindy, Smits, Evelien, Banham, Alison H., Mills, Ken I., Orchard, Kim and Guinn, Barbara Ann (2018) Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia. Oncotarget, 9 (3), 3853-3866. (doi:10.18632/oncotarget.23380).

Record type: Article

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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Accepted/In Press date: 26 November 2017
e-pub ahead of print date: 17 December 2017
Published date: 2018
Keywords: Acute lymphocytic leukemia, Antigen identification, Immunotherapy, Survivin, WT1

Identifiers

Local EPrints ID: 417476
URI: https://eprints.soton.ac.uk/id/eprint/417476
ISSN: 1949-2553
PURE UUID: dee2819c-58c4-4d4c-8fa3-ab039b897b39
ORCID for Kim Orchard: ORCID iD orcid.org/0000-0003-2276-3925

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Date deposited: 01 Feb 2018 17:30
Last modified: 16 Feb 2018 17:30

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Contributors

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

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