RNA methylation sequencing shows different gene expression signatures for response to azacytidine therapy in high-grade myelodysplastic syndromes.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE

Publication: Oxford, England : Wiley-Blackwell
Original Publication: Bucharest : "Carol Davila" University Press, 2000-

Myelodysplastic Syndromes*/genetics ; Myelodysplastic Syndromes*/drug therapy ; Myelodysplastic Syndromes*/pathology ; Azacitidine*/pharmacology ; Azacitidine*/therapeutic use ; DNA Methylation*/drug effects; Humans ; Female ; Aged ; Male ; Middle Aged ; Transcriptome/genetics ; Transcriptome/drug effects ; Aged, 80 and over ; Epigenesis, Genetic/drug effects ; Sequence Analysis, RNA ; Antimetabolites, Antineoplastic/therapeutic use ; Antimetabolites, Antineoplastic/pharmacology ; Prognosis ; High-Throughput Nucleotide Sequencing ; Gene Expression Profiling ; RNA Methylation

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.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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Keywords: RNA methylation sequencing; myelodysplastic syndromes; prognosis

M801H13NRU (Azacitidine)
0 (Antimetabolites, Antineoplastic)

Date Created: 20240928 Date Completed: 20240928 Latest Revision: 20240930

20240930

PMC11436316

10.1111/jcmm.70078

39334509