RNA methylation sequencing shows different gene expression signatures for response to azacytidine therapy in high-grade myelodysplastic syndromes
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články
PubMed
39334509
PubMed Central
PMC11436316
DOI
10.1111/jcmm.70078
Knihovny.cz E-zdroje
- Klíčová slova
- RNA methylation sequencing, myelodysplastic syndromes, prognosis,
- MeSH
- azacytidin * farmakologie terapeutické užití MeSH
- epigeneze genetická účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylace RNA MeSH
- metylace DNA * účinky léků MeSH
- myelodysplastické syndromy * genetika farmakoterapie patologie MeSH
- prognóza MeSH
- protinádorové antimetabolity terapeutické užití farmakologie MeSH
- sekvenční analýza RNA MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transkriptom genetika účinky léků MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- azacytidin * MeSH
- protinádorové antimetabolity 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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