DNA Methylation Events as Markers for Diagnosis and Management of Acute Myeloid Leukemia and Myelodysplastic Syndrome

Abstract

During the onset and progression of hematological malignancies, many changes occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in promoter regions. DNA methylation is an epigenetic modification that regulates gene expression and is a key event for tumorigenesis. The continuous search for biomarkers that signal early disease, indicate prognosis, and act as therapeutic targets has led to studies investigating the role of DNA in cancer onset and progression. This review focuses on DNA methylation changes as potential biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in acute myeloid leukemia and myelodysplastic syndrome. Here, we report that distinct changes in DNA methylation may alter gene function and drive malignant cellular transformation during several stages of leukemogenesis. Most of these modifications occur at an early stage of disease and may predict myeloid/lymphoid transformation or response to therapy, which justifies its use as a biomarker for disease onset and progression. Methylation patterns, or its dynamic change during treatment, may also be used as markers for patient stratification, disease prognosis, and response to treatment. Further investigations of methylation modifications as therapeutic biomarkers, which may correlate with therapeutic response and/or predict treatment toxicity, are still warranted.

Caffeic acid and chlorogenic acid cytotoxicity, genotoxicity and impact on global DNA methylation in human leukemic cell lines

“…Epigenetic dysregulation, such as DNA hypo-or hypermethylation, is closely associated with the development and progression of hematological malignancies. Alterations in the cellular epigenome, such as impaired DNA methylation mediated by DNA methyltransferases, play important roles in tumorigenesis of acute myeloid leukemia and acute lymphoblastic leukemia (Dexheimer et al, 2017;Helmer et al, 2019).…”

Global methylation in relation to methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

“…Currently, no studies on changes in DNA methylation in relation to the development of chemotherapy-related oral mucositis exist. However, DNA methylation has been implicated as a possible biomarker of treatment-related toxicity in other malignancies and rheumathoid arthritis treatment [ 13 – 16 ].…”

Rapamycin ameliorates psoriasis by regulating the expression and methylation levels of tropomyosin viaERK1/2 andmTORpathways in vitro and in vivo

“…It is well known that the most of gene expression could be inhibited during DNA methylation. Therefore, DNA methylation has been considered as a gene regulating mechanism and involved in various physiological processes, including epigenetic silence, X‐chromosome inactivation and so on . Aberrant expression and methylation levels of TPMs were often found in various human diseases; however, whether the expression and methylation of TPMs are involved in the psoriasis remains unknown.…”