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Updated: Oct 6, 2025
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Characterization of m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration
Shiyu Han1,2,3,4,5, Jiaqian Qi1,2,3,4, Kun Fang1,2,3
1National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Background:
Previous studies have confirmed the existence of epigenetic regulation of immune responses in acute myeloid leukemia. However, the potential role of RNA N6-methyladenosine (m6A) remodeling in tumor microenvironment (TME) infiltration remains unclear.
Methods And Materials:
m6A patterns of 469 AML patients (420 of which provided survival data) based on 18 m6A regulators were systematically evaluated. Based on the expression of 18 m6A regulators, unsupervised agglomerative cluster analysis was applied to recognize the various m6A modification types and to classify patients. We linked these patterns to TME infiltration characteristics and identified three distinct populations of m6A modifications.
Results:
These three TME cell infiltration patterns are characterized by a high degree of concordance with the three tumor immunophenotypes, which include immunoinflammatory, immunorejection, and immune inert patterns. We showed that assessment of m6A modification patterns within individually neoplasms can forecast the stage of neoplasmic inflammation, TME basal activity, subtype, hereditary mutation, and clinical patient prognosis. Limited low m6Ascore, featuring increased mutational load and immune activation, indicates an inflammatory phenotype of TME with a 5-year survival rate at 14.4% compared to the high-m6Ascore group (40.9%).
Conclusions:
Data from two different cohorts demonstrated that a higher m6Ascore showed a marked therapeutic superiority as well as clinical advantage. Assessing m6A modification patterns in AML patients could improve our knowledge of the TME infiltrative profile as well as directing effective immunotherapeutic approaches.
Insights
RNA N6-methyladenosine (m6A) remodeling influences acute myeloid leukemia (AML) tumor microenvironment (TME) infiltration. Distinct m6A patterns correlate with TME phenotypes and patient prognosis, guiding potential immunotherapeutic strategies.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Epigenetic regulation of immune responses in acute myeloid leukemia (AML) is established.
- The role of RNA N6-methyladenosine (m6A) remodeling in tumor microenvironment (TME) infiltration in AML is not well understood.
Purpose of the Study:
- To investigate the association between m6A modification patterns and TME infiltration characteristics in AML.
- To explore the prognostic value of m6A patterns in AML patients.
Main Methods:
- Systematic evaluation of m6A patterns based on 18 m6A regulators in 469 AML patients.
- Unsupervised agglomerative cluster analysis to classify patients into distinct m6A modification types.
- Correlation analysis between m6A patterns and TME infiltration characteristics.
Main Results:
- Three distinct m6A modification patterns were identified, showing high concordance with tumor immunophenotypes (immunoinflammatory, immunorejection, immune inert).
- m6A modification patterns can predict neoplasm inflammation, TME activity, subtype, mutations, and patient prognosis.
- A low m6Ascore (inflammatory TME) was associated with a 5-year survival rate of 14.4%, versus 40.9% for the high m6Ascore group.
Conclusions:
- Higher m6Ascore demonstrates therapeutic superiority and clinical advantage in AML patients across two cohorts.
- Assessing m6A modification patterns enhances understanding of TME infiltration in AML.
- m6A patterns can guide the development of effective immunotherapeutic approaches for AML.
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