RNA methylation sequencing shows different gene expression signatures for response to azacytidine therapy in high-grade myelodysplastic syndromes
Language English Country Great Britain, England Media print
Document type Journal Article
PubMed
39334509
PubMed Central
PMC11436316
DOI
10.1111/jcmm.70078
Knihovny.cz E-resources
- Keywords
- RNA methylation sequencing, myelodysplastic syndromes, prognosis,
- MeSH
- Azacitidine * pharmacology therapeutic use MeSH
- Epigenesis, Genetic drug effects MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA Methylation MeSH
- DNA Methylation * drug effects MeSH
- Myelodysplastic Syndromes * genetics drug therapy pathology MeSH
- Prognosis MeSH
- Antimetabolites, Antineoplastic therapeutic use pharmacology MeSH
- Sequence Analysis, RNA MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Transcriptome genetics drug effects MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Azacitidine * MeSH
- Antimetabolites, Antineoplastic MeSH
Myelodysplastic syndromes (MDS) are myeloid malignancies with heterogeneous genotypes and phenotypes, characterized by ineffective haematopoiesis and a high risk of progression towards acute myeloid leukaemia (AML). Prognosis for patients treated with hypomethylating agents (HMAs), as is azacytidine, the main drug used as frontline therapy for MDS is mostly based on cytogenetics and next generation sequencing (NGS) of the initial myeloid clone. Although the critical influence of the epigenetic landscape upon cancer cells survival and development as well on tumour environment establishment is currently recognized and approached within current clinical practice in MDS, the heterogenous response of the patients to epigenetic therapy is suggesting a more complex mechanism of action, as is the case of RNA methylation. In this sense, the newly emerging field of epitranscriptomics could provide a more comprehensive perspective upon the modulation of gene expression in malignancies, as is the proof-of-concept of MDS. We initially did RNA methylation sequencing on MDS patients (n = 6) treated with azacytidine and compared responders with non-responders. Afterwards, the genes identified were assessed in vitro and afterwards validated on a larger cohort of MDS patients treated with azacytidine (n = 58). Our data show that a more accurate prognosis could be based on analysing the methylome and thus we used methylation sequencing to differentially split high-grade MDS patients with identical demographical and cytogenetic features, between azacytidine responders and non-responders.
Department of Hematology Ion Chiricuta Clinical Cancer Center Cluj Napoca Romania
Department of Hematology Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca Romania
Department of Internal Medicine 2 Hematology University Hospital Würzburg Würzburg Germany
Department of Oncology Bistrita Emergency Hospital Bistrita Romania
Laboratory of Anemias Institute of Hematology and Blood Transfusion Prague Czech Republic
University Hospital and University of Zurich Zurich Switzerland
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