Single-cell transcriptome profiling of m6A regulator-mediated methylation modification patterns in elderly acute myeloid leukemia patients

作者：Zhe Wang, Xin Du, Peidong Zhang, Meiling Zhao, Tianbo Zhang, Jiang Liu, Xiaolan Wang, Doudou Chang, Xiaxia Liu, Sicheng Bian, Xialin Zhang, Ruijuan Zhang · 发表于：Molecular Biomedicine · 年份：2024 · DOI：10.1186/s43556-024-00234-7 · 被引用次数：5 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

Abstract Millions of people worldwide die of acute myeloid leukaemia (AML) each year. Although N6-methyladenosine (m 6 A) modification has been reported to regulate the pathogenicity of AML, the mechanisms by which m 6 A induces dysfunctional hematopoietic differentiation in elderly AML patients remain elusive. This study elucidates the mechanisms of the m 6 A landscape and the specific roles of m 6 A regulators in hematopoietic cells of elderly AML patients. Notably, fat mass and obesity-associated protein ( FTO ) was found to be upregulated in hematopoietic stem cells (HSCs), myeloid cells, and T-cells, where it inhibits their differentiation via the WNT signaling pathway. Additionally, elevated YT521-B homology domain family proteins 2 ( YTHDF2 ) expression in erythrocytes was observed to negatively regulate differentiation through oxidative phosphorylation, resulting in leukocyte activation. Moreover, IGF2BP2 was significantly upregulated in myeloid cells, contributing to an aberrant chromosomal region and disrupted oxidative phosphorylation. m 6 A regulators were shown to induce abnormal cell-cell communication within hematopoietic cells, mediating ligand-receptor interactions across various cell types through the HMGB1-mediated pathway, thereby promoting AML progression. External validation was conducted using an independent single-cell RNA sequencing (scRNA-Seq) dataset. The THP-1 and MV411 cell lines were utilized to corroborate the m 6 A regulator profile; in vitro e...