Epigenetic therapy in AML: network redundancy, resistance, and non-coding RNAs
- 1Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Ceará
- 2Oswaldo Cruz Foundation - Fiocruz Ceara
Abstract
Acute myeloid leukemia (AML) remains an aggressive hematologic malignancy sustained by dynamic epigenetic networks integrating DNA methylation, histone modifications, and ncRNA-linked chromatin-associated mechanisms. Collectively, these mechanisms enforce leukemic self-renewal, differentiation arrest, and therapeutic adaptation. Hypomethylating agents, IDH1/2 and menin inhibitors, and emerging chromatin-directed drugs have established epigenetic vulnerabilities as actionable therapeutic targets across genetically defined AML subsets. However, most clinical responses remain partial and transient, frequently limited by therapeutic resistance, functional redundancy within the epigenomic landscape, and the clonal plasticity that characterizes AML progression. This review synthesizes current evidence on how genetic context shapes epigenetic dependencies, therapeutic performance, and resistance mechanisms of established and emerging epigenetic therapies, with particular emphasis on the DNA methylation axis and chromatin/transcriptional complex-directed strategies. Within this framework, selected non-coding RNAs (ncRNAs) are considered as context-dependent modulators and potential biomarkers that intersect with epigenetic programs in specific settings, rather than as a separate epigenetic layer. Durable disease control will likely require rational combinations guided by biomarker-driven patient selection and integrated monitoring of epigenetic reprogramming, while ncRNA-based readouts may complement genomic and epigenomic markers in defined AML subsets.
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BibTeX
@article{fernandes2026epigenetic,
title = {{Epigenetic therapy in AML: network redundancy, resistance, and non-coding RNAs}},
author = {Maria da Conceição Rodrigues Fernandes and Thalita Basso Scandolara and Jéssica Almeida Mota and Mariana Palmeira Manso and Gilvan Pessoa Furtado and Sarah Sant’anna Maranhão and Claudia do Ó Pessoa and Cristiana Libardi Miranda Furtado},
journal = {Epigenetics Communications},
year = {2026},
month = oct,
doi = {10.1186/s43682-026-00054-6},
url = {https://doi.org/10.1186/s43682-026-00054-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Epigenetic therapy in AML: network redundancy, resistance, and non-coding RNAs
AU - Maria da Conceição Rodrigues Fernandes
AU - Thalita Basso Scandolara
AU - Jéssica Almeida Mota
AU - Mariana Palmeira Manso
AU - Gilvan Pessoa Furtado
AU - Sarah Sant’anna Maranhão
AU - Claudia do Ó Pessoa
AU - Cristiana Libardi Miranda Furtado
PY - 2026
DA - 2026/10/25
JO - Epigenetics Communications
DO - 10.1186/s43682-026-00054-6
UR - https://doi.org/10.1186/s43682-026-00054-6
AB - Acute myeloid leukemia (AML) remains an aggressive hematologic malignancy sustained by dynamic epigenetic networks integrating DNA methylation, histone modifications, and ncRNA-linked chromatin-associated mechanisms. Collectively, these mechanisms enforce leukemic self-renewal, differentiation arrest, and therapeutic adaptation. Hypomethylating agents, IDH1/2 and menin inhibitors, and emerging chromatin-directed drugs have established epigenetic vulnerabilities as actionable therapeutic targets across genetically defined AML subsets. However, most clinical responses remain partial and transient, frequently limited by therapeutic resistance, functional redundancy within the epigenomic landscape, and the clonal plasticity that characterizes AML progression. This review synthesizes current evidence on how genetic context shapes epigenetic dependencies, therapeutic performance, and resistance mechanisms of established and emerging epigenetic therapies, with particular emphasis on the DNA methylation axis and chromatin/transcriptional complex-directed strategies. Within this framework, selected non-coding RNAs (ncRNAs) are considered as context-dependent modulators and potential biomarkers that intersect with epigenetic programs in specific settings, rather than as a separate epigenetic layer. Durable disease control will likely require rational combinations guided by biomarker-driven patient selection and integrated monitoring of epigenetic reprogramming, while ncRNA-based readouts may complement genomic and epigenomic markers in defined AML subsets.
SN - 2730-7034
ER -