The prognostic significance of global aberrant alternative splicing in patients with myelodysplastic syndrome
Open accessAbstract
Aberrant alternative splicing (AS) is a hallmark of cancer development. However, there are limited data regarding its clinical implications in myelodysplastic syndrome (MDS). In this study, we performed an in-depth analysis of global AS in 176 primary MDS patients with 20 normal marrow transplant donors as reference. We found that 26.9% of the expressed genes genome-wide were aberrantly spliced in MDS patients compared with normal donors. These aberrant AS genes were related to pathways involved in cell proliferation, cell adhesion and protein degradation. A higher degree of global aberrant AS was associated with male gender and U2AF1 mutation, and predicted shorter overall survival and time to leukemic change. Moreover, it was an independent unfavorable prognostic factor irrespective of age, revised international prognostic scoring system (IPSS-R) risk, and mutations in SRSF2, ZRSR2, ASXL1, TP53, and EZH2. With LASSO-Cox regression method, we constructed a simple prognosis prediction model composed of 13 aberrant AS genes, and demonstrated that it could well stratify MDS patients into distinct risk groups. To our knowledge, this is the first report demonstrating significant prognostic impacts of aberrant splicing on MDS patients. Further prospective studies in larger cohorts are needed to confirm our observations.
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Alternative splicing abnormalities play a pivotal role in leukemia pathogenesis.
“Current evidence suggests a pivotal role of alternative splicing abnormalities in leukemia pathogenesis (12,13).”
From Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias (2021) · cites this paper as [12]
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Mäkelä, E., Pavic, K., Varila, T., Salmenniemi, U., Löyttyniemi, E., Nagelli, S. G., Ammunét, T., Kähäri, V.-M., Clark, R. E., Elo, L. L., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3679 · Cited by 18 · see citing works
- Authors
- Yang, Y.-T., Chiu, Y.-C., Kao, C.-J., Hou, H.-A., Lin, C.-C., Tsai, C.-H., Tseng, M.-H., Chou, W.-C., & Tien, H.-F.
- Affiliations
- National Taiwan University (TW)
- The University of Texas at San Antonio Health Science Center (US)
- National Taiwan University Hospital (TW)
- Corresponding author
- Chou, Wen-Chien
- Tien, Hwei-Fang
- ORCID
- Venue
- Blood Cancer Journal
- Published
- 2018-08-13
- Volume
- 8
- Issue
- 8
- Pages
- 78-78
- ISSN
- 2044-5385 (ISSN-L)
- PMC
- PMC6089879
- OpenAlex
- W2885476743
- Cited by
- 32
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 5
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Blood Cancer Journal (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Council
- Ministry of Science and Technology, Taiwan (MOST106-2314-B002-231, 130-MY3, 2314-B-002, MOHW106-TDU-B-211-144005, MOST104-2923-B002-001)
- National Health Research Institutes
- National Taiwan University Hospital (MOHW103-TD-B-111-04, UN103-051, NTUH 102P06)
- National Taiwan University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- myelodysplastic syndrome, prognostic factors, overall survival, U2AF1 mutation, prognostic stratification, prognostic gene signature, LASSO Cox regression, cell proliferation, cell adhesion, protein degradation
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Myelodysplastic Syndromes, Prognosis, Reproducibility of Results, Biomarkers, Proportional Hazards Models, Alternative Splicing, Computational Biology, Gene Expression Profiling, Kaplan-Meier Estimate, Transcriptome
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