ArticleCell death & disease2018
Mutations in the P10 region of procaspase-8 lead to chemotherapy resistance in acute myeloid leukemia by impairing procaspase-8 dimerization.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Arginine methylation of caspase-8 controls life/death decisions in extrinsic apoptotic networks.Oncogene · 2024Article
- Caspase 8 deletion causes infection/inflammation-induced bone marrow failure and MDS-like disease in mice.Cell death & disease · 2024Article
- Review
- A novel PTEN mutant caused by polymorphism in cis-regulatory elements is involved in chemosensitivity in breast cancer.American journal of cancer research · 2023Article
- Lnc-ATG9B-4 aggravates progress of hepatocellular carcinoma through cell proliferation and migration by upregulating CDK5.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- The role of multiple metabolic genes in predicting the overall survival of colorectal cancer: A study based on TCGA and GEO databases.PloS one · 2021Article
- Caspase-8 Induces Lysosome-Associated Cell Death in Cancer Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- The multiple-kinase inhibitor lenvatinib inhibits the proliferation of acute myeloid leukemia cells.Animal models and experimental medicine · 2019Article
- Emerging Therapies for Acute Myelogenus Leukemia Patients Targeting Apoptosis and Mitochondrial Metabolism.Cancers · 2019Review
- Pharmacogenetics of hepatocellular carcinoma and cholangiocarcinoma.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Identification of a NovelBioMed research international · 2019Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caspase-8 activation initiates apoptotic signaling cascades, and certain mutations in procasepase-8 have been reported to be associated with the progression and prognosis of different types of tumors. In this study, we have identified four novel mutations, which are highly correlated with chemotherapy resistance and poor prognosis of acute myeloid leukemia (AML) patients, within the P10 subunit of procaspase-8. These newly discovered mutations cause premature termination of translation, resulting in truncated procaspase-8 protein, which is incapable of forming dimer to initiate apoptosis signaling pathway. Further biochemical analysis reveals that the segment of P10 subunit of procaspase-8 consisting of three amino acid residues from L491 to F493 is crucial for the formation of procaspase-8 interdimer, and the aberration of this segment disrupts the dimerization and consequently precludes the activation of caspase-8 and downstream apoptotic signaling pathway. Therefore, the patients with AML who bear these types of P10 mutations were more likely to develop chemotherapy resistance due to impaired apoptotic signaling in cellular system, leading to significantly reduced overall survival (OS) as compared with patients carrying no such types of P10 mutations. Taken together, these newly identified P10 mutations in procaspase-8 could be used as novel biomarkers for predicting response and survival of chemotherapy-treated AML patients, as well as potential therapeutic targets for medical intervention in the future.
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