Comprehensive analysis of m6A methylome alterations after azacytidine plus venetoclax treatment for acute myeloid leukemia by nanopore sequencing

Zhang, Zaifeng; Zhang, Lili; Li, Jiangtao; Feng, Ru; Li, Chang; Liu, Ye; Sun, Gaoyuan; Xiao, Fei; Zhang, Chunli

doi:10.1016/j.csbj.2024.02.029

Computational and Structural Biotechnology Journal

2024

DOI: 10.1016/j.csbj.2024.02.029

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Comprehensive analysis of m6A methylome alterations after azacytidine plus venetoclax treatment for acute myeloid leukemia by nanopore sequencing

Zaifeng Zhang,

Lili Zhang,

Jiangtao Li

et al.

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2024

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Cited by 2 publications

References 60 publications

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mRNA m5C Alteration in Azacitidine Demethylation Treatment of Acute Myeloid Leukemia

Chen,

Guo,

Zhang

et al. 2024

Molecular Carcinogenesis

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The DNA demethylating therapy with azacitidine (AZA) is a promising therapeutic strategy for elderly patients with acute myeloid leukemia (AML). AZA primarily inhibits DNA methylation, promotes cell differentiation and apoptosis in AML. However, as a cytosine nucleoside analog, AZA also has the potential to be incorporated into RNA molecules. To assess the impact of AZA on RNA m5C methylation during demethylating therapy, we conducted Nanopore direct‐RNA sequencing on samples from three AML patients pre and after demethylating therapy, as well as on HL‐60 cells pretreated with AZA. We performed an integrated analysis of the transcriptome and the m5C methylome, contrasting the states of complete remission with those of active disease (AML). Our results revealed an extensive demethylation effect at the RNA level attributable to AZA and found that mRNA m5C modification may play a pivotal role in the progression of AML. Additionally, S100P was identified as a biomarker with significant prognostic implications. We also conducted a conjoint analysis of the transcriptome and the m5C methylome of the full‐length transcripts, uncovering several dysregulated mRNA isoforms. Collectively, our findings indicate that mRNA m5C methylation is implicated during AML progression, and AZA exhibits an overall suppressive effect on this process.

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mRNA m5C Alteration in Azacitidine Demethylation Treatment of Acute Myeloid Leukemia

Chen,

Guo,

Zhang

et al. 2024

Molecular Carcinogenesis

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Current insights on m6A RNA modification in acute leukemia: therapeutic targets and future prospects

Kaur,

Sharma,

Bhatia

et al. 2024

Front. Oncol.

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RNA modification is the critical mechanism for regulating post-transcriptional processes. There are more than 150 RNA modifications reported so far, among which N6-Methyladenosine is the most prevalent one. M6A RNA modification complex consists of ‘writers’, ‘readers’ and ‘erasers’ which together in a group catalyze, recognize and regulate the methylation process of RNA and thereby regulate the stability and translation of mRNA. The discovery of erasers also known as demethylases, revolutionized the research on RNA modifications as it revealed that this modification is reversible. Since then, various studies have focused on discovering the role of m6A modification in various diseases especially cancers. Aberrant expression of these ‘readers’, ‘writers’, and ‘erasers’ is found to be altered in various cancers resulting in disturbance of cellular homeostasis. Acute leukemias are the most common cancer found in pediatric patients and account for 20% of adult cases. Dysregulation of the RNA modifying complex have been reported in development and progression of hematopoietic malignancies. Further, targeting m6A modification is the new approach for cancer immunotherapy and is being explored extensively. This review provides detailed information about current information on the role of m6A RNA modification in acute leukemia and their therapeutic potential.

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Comprehensive analysis of m6A methylome alterations after azacytidine plus venetoclax treatment for acute myeloid leukemia by nanopore sequencing

Cited by 2 publications

References 60 publications

mRNA m5C Alteration in Azacitidine Demethylation Treatment of Acute Myeloid Leukemia

mRNA m5C Alteration in Azacitidine Demethylation Treatment of Acute Myeloid Leukemia

Current insights on m6A RNA modification in acute leukemia: therapeutic targets and future prospects

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