Acute myeloid leukemia (AML) is a complex hematologic cancer marked by both genetic and epigenetic abnormalities that lead to the expansion of immature myeloid cells and a block in their normal differentiation. Among the various molecular mechanisms implicated in its pathogenesis, epigenetic alterations have gained increasing attention for their crucial role in initiating and sustaining leukemic transformation. Mutations in key epigenetic regulators such as DNMT3A, TET2, IDH1/2, and EZH2 have been frequently identified in AML, contributing to widespread disruptions in DNA methylation patterns, histone modification states, and chromatin structure. These changes profoundly influence gene expression programs by favoring malignant progression. Unlike permanent genetic mutations, epigenetic changes are potentially reversible, making them particularly appealing as therapeutic targets. Agents that modulate the epigenome, such as DNA hypomethylating drugs or other epi-drugs, have shown significant clinical activity, especially in older patients or those medically unsuitable for intensive chemotherapy. Additionally, novel compounds are being actively evaluated, both alone and in combination with existing therapies. Overall, the epigenetic landscape of AML offers valuable opportunities for innovative treatment approaches. Ongoing research is crucial to better understand resistance mechanisms, define predictive biomarkers, and refine therapeutic strategies aimed at improving clinical outcomes for AML patients.
Unraveling the Involvement of Epigenetics in Acute Myeloid Leukemia (AML): Focusing on Epigenetic Treatments in AML
Antonio Beato;Gregorio Favale;Daniela Carannante;Lucia Altucci;Vincenzo Carafa
2026
Abstract
Acute myeloid leukemia (AML) is a complex hematologic cancer marked by both genetic and epigenetic abnormalities that lead to the expansion of immature myeloid cells and a block in their normal differentiation. Among the various molecular mechanisms implicated in its pathogenesis, epigenetic alterations have gained increasing attention for their crucial role in initiating and sustaining leukemic transformation. Mutations in key epigenetic regulators such as DNMT3A, TET2, IDH1/2, and EZH2 have been frequently identified in AML, contributing to widespread disruptions in DNA methylation patterns, histone modification states, and chromatin structure. These changes profoundly influence gene expression programs by favoring malignant progression. Unlike permanent genetic mutations, epigenetic changes are potentially reversible, making them particularly appealing as therapeutic targets. Agents that modulate the epigenome, such as DNA hypomethylating drugs or other epi-drugs, have shown significant clinical activity, especially in older patients or those medically unsuitable for intensive chemotherapy. Additionally, novel compounds are being actively evaluated, both alone and in combination with existing therapies. Overall, the epigenetic landscape of AML offers valuable opportunities for innovative treatment approaches. Ongoing research is crucial to better understand resistance mechanisms, define predictive biomarkers, and refine therapeutic strategies aimed at improving clinical outcomes for AML patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
