Bibliographic Details
| Title: |
High iASPP (PPP1R13L) expression is an independent predictor of adverse clinical outcome in acute myeloid leukemia (AML) |
| Authors: |
Mihada Bajrami Saipi, Alessia Ruiba, Marcus Matthias Schittenhelm, Gunnar Blumenstock, Balázs Győrffy, Serena Fazio, Marlon Hafner, Anna-Lena Ahrens, Lara Aldinger, Vanessa Aellig, François G. Kavelaars, César Nombela-Arrieta, Falko Fend, Peter J. M. Valk, Driessen Christoph, Kerstin Maria Kampa-Schittenhelm |
| Source: |
Cell Death and Disease, Vol 15, Iss 11, Pp 1-13 (2024) |
| Publisher Information: |
Nature Publishing Group, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
Abstract Apoptosis-stimulating proteins of p53 (ASPPs) are a family of proteins that modulate key tumor suppressor pathways via direct interaction with p53. Deregulation of these proteins promotes cancer development and impairs sensitivity to systemic (chemo)therapy and radiation. In this study, we describe that the inhibitor of ASPP (iASPP) is frequently highly expressed in acute myeloid leukemia (AML) and that overexpression correlates with a poor clinical outcome. Four independent patient cohorts comprising about 1500 patient samples were analysed and consistently confirm an association of high iASPP expression with unfavourable clinical characteristics and shorter survival. Notably, the predictive role of iASPP is independent of, and adds information to, the European LeukemiaNET (ELN) risk classification. iASPP-interference cell models were developed to investigate the underlying functional aspects of iASPP in AML biology. Attenuation of iASPP expression resulted in reduced proliferation rates of leukemic blasts and rendered cells more susceptible towards induction of apoptosis in response to cytotoxic therapy. In line, independent NSG xenograft mouse experiments demonstrate that attenuation of iASPP results in a significant delay of disease onset and tumor burden and this translates to longer overall survival of mice. In conclusion, deregulation of iASPP has direct functional consequences in AML. Determination of iASPP expression levels provides valuable additional information as a predictive marker in AML and may guide treatment decisions. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-024-07190-8 |
| Access URL: |
https://doaj.org/article/793637dff01642d6878a7b3b72ca88da |
| Accession Number: |
edsdoj.793637dff01642d6878a7b3b72ca88da |
| Database: |
Directory of Open Access Journals |
