Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications

Yang, Xian‐Wen; Wong, Molly Pui Man; Ng, Ray Kit

doi:10.3390/ijms20184576

Cited by 70 publications

(52 citation statements)

References 141 publications

(185 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, hypermethylation of the retinoblastoma gene promoter region has been observed in a significant number of unilateral retinoblastoma cancers (Robertson, 2001). Dysregulation of DNMT activity, and subsequent hypermethylation of promoter regions, has been identified as a key component in acute myeloid leukemia initiation and progression (Yang et al, 2019). Furthermore, hypermethylation of promoter regions has also been observed in 56% of breast and 15-30% ovarian cancers (de Almeida et al, 2019;Hentze et al, 2019).…”

Section: Parp Inhibitors and Drugs Targeting Epigenetic Modificationsmentioning

confidence: 99%

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

Rose

Burgess

O’Byrne

et al. 2020

Front. Cell Dev. Biol.

445

296

View full text Add to dashboard Cite

The Poly (ADP-ribose) polymerase (PARP) family has many essential functions in cellular processes, including the regulation of transcription, apoptosis and the DNA damage response. PARP1 possesses Poly (ADP-ribose) activity and when activated by DNA damage, adds branched PAR chains to facilitate the recruitment of other repair proteins to promote the repair of DNA single-strand breaks. PARP inhibitors (PARPi) were the first approved cancer drugs that specifically targeted the DNA damage response in BRCA1/2 mutated breast and ovarian cancers. Since then, there has been significant advances in our understanding of the mechanisms behind sensitization of tumors to PARP inhibitors and expansion of the use of PARPi to treat several other cancer types. Here, we review the recent advances in the proposed mechanisms of action of PARPi, biomarkers of the tumor response to PARPi, clinical advances in PARPi therapy, including the potential of combination therapies and mechanisms of tumor resistance.

show abstract

Section: Parp Inhibitors and Drugs Targeting Epigenetic Modificationsmentioning

confidence: 99%

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

Rose

Burgess

O’Byrne

et al. 2020

Front. Cell Dev. Biol.

445

296

View full text Add to dashboard Cite

show abstract

“…It is closely related to tumors by silencing tumor suppressor genes and activating oncogenes by high/low methylation (7). Abnormal DNA methylation is considered a hallmark of AML and is considered a powerful epigenetic marker in early diagnosis, prognosis prediction, and treatment decision making (8).…”

Section: Introductionmentioning

confidence: 99%

DNA methylation-based prognostic biomarkers of acute myeloid leukemia patients

Gao

Shi

et al. 2019

Ann Transl Med

View full text Add to dashboard Cite

Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disease that prevents normal myeloid differentiation with its common features. Its incidence increases with age and has a poor prognosis.Studies have shown that DNA methylation and abnormal gene expression are closely related to AML. Methods:The methylation array data and mRNA array data are from the Gene Expression Omnibus (GEO) database. Through the GEO data, we identified differential genes from tumors and normal samples. Then we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses on these differential genes. Protein-protein interaction (PPI) network construction and module analysis were performed to screen the highest-scoring modules. Next, we used SurvExpress software to analyze the genes in the highest-scoring module and selected potential prognostic genes by univariate and multivariate Cox analysis. Finally, the three genes screened by SurvExpress software were analyzed using the methylation analysis site MethSurv to explore AML associated methylation biomarkers. Results:We found three genes that can be used as independent prognostic factors for AML. These three genes are the low expression/methylation genes ATP11A and ITGAM, and the high expression/low methylation gene ZNRF2.Conclusions: In this study, we performed a comprehensive analysis of DNA methylation and gene expression to identify key epigenetic genes in AML.

show abstract

“…For lymphatic and hematopoietic neoplasms, blood is a much more readily available biospecimen, providing a ready opportunity to identify markers that can detect cancer in early stages of development. Global DNA hypomethylation has been associated with better clinical outcomes in acute lymphoblastic leukemia [9] and acute myeloid leukemia [10,11], and has also been used to conduct genetic characterization for stratification of acute myeloid leukemia risk groups [12]. In addition, site-specific differential blood DNA methylation in humans has been identified in several epigenomewide association studies for multiple myeloma [13], B-cell lymphoma [14] and chronic lymphocytic leukemia [15], and in vitro for T-acute lymphoblastic leukemia [16].…”

Section: Introductionmentioning

confidence: 99%

DNA methylation and cancer incidence: lymphatic–hematopoietic versus solid cancers in the Strong Heart Study

et al. 2021

View full text Add to dashboard Cite

Background Epigenetic alterations may contribute to early detection of cancer. We evaluated the association of blood DNA methylation with lymphatic–hematopoietic cancers and, for comparison, with solid cancers. We also evaluated the predictive ability of DNA methylation for lymphatic–hematopoietic cancers. Methods Blood DNA methylation was measured using the Illumina Infinium methylationEPIC array in 2324 Strong Heart Study participants (41.4% men, mean age 56 years). 788,368 CpG sites were available for differential DNA methylation analysis for lymphatic–hematopoietic, solid and overall cancers using elastic-net and Cox regression models. We conducted replication in an independent population: the Framingham Heart Study. We also analyzed differential variability and conducted bioinformatic analyses to assess for potential biological mechanisms. Results Over a follow-up of up to 28 years (mean 15), we identified 41 lymphatic–hematopoietic and 394 solid cancer cases. A total of 126 CpGs for lymphatic–hematopoietic cancers, 396 for solid cancers, and 414 for overall cancers were selected as predictors by the elastic-net model. For lymphatic–hematopoietic cancers, the predictive ability (C index) increased from 0.58 to 0.87 when adding these 126 CpGs to the risk factor model in the discovery set. The association was replicated with hazard ratios in the same direction in 28 CpGs in the Framingham Heart Study. When considering the association of variability, rather than mean differences, we found 432 differentially variable regions for lymphatic–hematopoietic cancers. Conclusions This study suggests that differential methylation and differential variability in blood DNA methylation are associated with lymphatic–hematopoietic cancer risk. DNA methylation data may contribute to early detection of lymphatic–hematopoietic cancers.

show abstract

Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications

Cited by 70 publications

References 141 publications

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

DNA methylation-based prognostic biomarkers of acute myeloid leukemia patients

DNA methylation and cancer incidence: lymphatic–hematopoietic versus solid cancers in the Strong Heart Study

Contact Info

Product

Resources

About