Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients
Despite recent advances in therapies including immunotherapy, patients with acute myeloid leukaemia (AML) still experience relatively poor survival rates. The Inhibition of Apoptosis (IAP) family member, survivin, also known by its gene and protein name, Baculoviral IAP Repeat Containing 5 (BIRC5),...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10482 |
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| author | Jochen Greiner Elliott Brown Lars Bullinger Robert K. Hills Vanessa Morris Hartmut Döhner Ken I. Mills Barbara-ann Guinn |
| author_facet | Jochen Greiner Elliott Brown Lars Bullinger Robert K. Hills Vanessa Morris Hartmut Döhner Ken I. Mills Barbara-ann Guinn |
| author_sort | Jochen Greiner |
| collection | DOAJ |
| description | Despite recent advances in therapies including immunotherapy, patients with acute myeloid leukaemia (AML) still experience relatively poor survival rates. The Inhibition of Apoptosis (IAP) family member, survivin, also known by its gene and protein name, Baculoviral IAP Repeat Containing 5 (BIRC5), remains one of the most frequently expressed antigens across AML subtypes. To better understand its potential to act as a target for immunotherapy and a biomarker for AML survival, we examined the protein and pathways that BIRC5 interacts with using the Kyoto Encyclopedia of Genes and Genomes (KEGG), search tool for recurring instances of neighbouring genes (STRING), WEB-based Gene Set Analysis Toolkit, Bloodspot and performed a comprehensive literature review. We then analysed data from gene expression studies. These included 312 AML samples in the Microarray Innovations In Leukemia (MILE) dataset. We found a trend between above median levels of BIRC5 being associated with improved overall survival (OS) but this did not reach statistical significance (<i>p</i> = 0.077, Log-Rank). There was some evidence of a beneficial effect in adjusted analyses where above median levels of BIRC5 were shown to be associated with improved OS (<i>p</i> = 0.001) including in Core Binding Factor (CBF) patients (<i>p</i> = 0.03). Above median levels of BIRC5 transcript were associated with improved relapse free survival (<i>p</i> < 0.0001). Utilisation of a second large cDNA microarray dataset including 306 AML cases, again showed no correlation between BIRC5 levels and OS, but high expression levels of BIRC5 correlated with worse survival in inv(16) patients (<i>p</i> = 0.077) which was highly significant when datasets A and B were combined (<i>p</i> = 0.001). In addition, decreased BIRC5 expression was associated with better clinical outcome (<i>p</i> = 0.004) in AML patients exhibiting CBF mainly due to patients with inv(16) (<i>p</i> = 0.007). This study has shown that BIRC5 expression plays a role in the survival of AML patients, this association is not apparent when we examine CBF patients as a cohort, but when those with inv(16) independently indicating that those patients with inv(16) would provide interesting candidates for immunotherapies that target BIRC5. |
| first_indexed | 2024-03-10T07:00:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:09Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-b458887357264f16a83fb7784b890a7f2023-11-22T16:10:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191048210.3390/ijms221910482Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) PatientsJochen Greiner0Elliott Brown1Lars Bullinger2Robert K. Hills3Vanessa Morris4Hartmut Döhner5Ken I. Mills6Barbara-ann Guinn7Department of Internal Medicine, Diakonie Hospital Stuttgart, 70176 Stuttgart, GermanyDepartment of Biomedical Sciences, University of Hull, Hull HU6 7RX, UKDepartment of Hematology, Oncology and Tumor Immunology, Charité–Universitätsmedizin Berlin, 13353 Berlin, GermanyNuffield Department of Population Health, Richard Doll Building, University of Oxford, Oxford OX3 7LF, UKDepartment of Biomedical Sciences, University of Hull, Hull HU6 7RX, UKDepartment of Internal Medicine III, University of Ulm, Helmholtzstr. 10, 89081 Ulm, GermanyPatrick G. Johnson Centre for Cancer Research, Queen’s University Belfast, Lisburn Road, Belfast BT9 7AE, UKDepartment of Biomedical Sciences, University of Hull, Hull HU6 7RX, UKDespite recent advances in therapies including immunotherapy, patients with acute myeloid leukaemia (AML) still experience relatively poor survival rates. The Inhibition of Apoptosis (IAP) family member, survivin, also known by its gene and protein name, Baculoviral IAP Repeat Containing 5 (BIRC5), remains one of the most frequently expressed antigens across AML subtypes. To better understand its potential to act as a target for immunotherapy and a biomarker for AML survival, we examined the protein and pathways that BIRC5 interacts with using the Kyoto Encyclopedia of Genes and Genomes (KEGG), search tool for recurring instances of neighbouring genes (STRING), WEB-based Gene Set Analysis Toolkit, Bloodspot and performed a comprehensive literature review. We then analysed data from gene expression studies. These included 312 AML samples in the Microarray Innovations In Leukemia (MILE) dataset. We found a trend between above median levels of BIRC5 being associated with improved overall survival (OS) but this did not reach statistical significance (<i>p</i> = 0.077, Log-Rank). There was some evidence of a beneficial effect in adjusted analyses where above median levels of BIRC5 were shown to be associated with improved OS (<i>p</i> = 0.001) including in Core Binding Factor (CBF) patients (<i>p</i> = 0.03). Above median levels of BIRC5 transcript were associated with improved relapse free survival (<i>p</i> < 0.0001). Utilisation of a second large cDNA microarray dataset including 306 AML cases, again showed no correlation between BIRC5 levels and OS, but high expression levels of BIRC5 correlated with worse survival in inv(16) patients (<i>p</i> = 0.077) which was highly significant when datasets A and B were combined (<i>p</i> = 0.001). In addition, decreased BIRC5 expression was associated with better clinical outcome (<i>p</i> = 0.004) in AML patients exhibiting CBF mainly due to patients with inv(16) (<i>p</i> = 0.007). This study has shown that BIRC5 expression plays a role in the survival of AML patients, this association is not apparent when we examine CBF patients as a cohort, but when those with inv(16) independently indicating that those patients with inv(16) would provide interesting candidates for immunotherapies that target BIRC5.https://www.mdpi.com/1422-0067/22/19/10482BIRC5overall survivalsurvivinacute myeloid leukaemiaCore Binding Factor (CBF)inv(16) |
| spellingShingle | Jochen Greiner Elliott Brown Lars Bullinger Robert K. Hills Vanessa Morris Hartmut Döhner Ken I. Mills Barbara-ann Guinn Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients International Journal of Molecular Sciences BIRC5 overall survival survivin acute myeloid leukaemia Core Binding Factor (CBF) inv(16) |
| title | Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients |
| title_full | Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients |
| title_fullStr | Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients |
| title_full_unstemmed | Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients |
| title_short | Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients |
| title_sort | survivin acute myeloid leukaemia a personalised target for inv 16 patients |
| topic | BIRC5 overall survival survivin acute myeloid leukaemia Core Binding Factor (CBF) inv(16) |
| url | https://www.mdpi.com/1422-0067/22/19/10482 |
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