DNA methylation: a saga of genome maintenance in hematological perspective

Chattopadhyaya, Saran; Ghosal, Somnath

doi:10.1007/s13577-022-00674-9

Cited by 18 publications

(10 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DNMT3A gene on 2q23, along with its product DNMT3A, dimerizes with DNMT3B, which is involved in de novo DNA methylation, by transferring methyl groups to the cytosine nucleotides at the CpG region 56 . DNMT3A mutations are detected in approximately 10% of MDSs and are associated with an increased incidence of progression to AML, likely driving the inferior overall survival (OS) associated with DNMT3A -mutated MDSs, including after hematopoietic stem cell transplant 3,57–59 …”

Section: Epidemiology Of Mds and Mds Precursor Conditionsmentioning

confidence: 99%

Epidemiology and Pathogenesis of Myelodysplastic Syndrome

Rotter,

Shimony,

Ling

et al. 2023

Cancer J

View full text Add to dashboard Cite

Myelodysplastic syndrome (MDS) is a clonal disorder characterized by ineffective hematopoiesis and variable cytopenias with a considerable risk of progression to acute myeloid leukemia. Epidemiological assessment of MDS remains challenging because of evolving classification systems, but the overall incidence in the United States is estimated to be approximately 4 per 100,000 and increases with age. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis (CH) to CH of indeterminate potential, clonal cytopenia of unknown significance, to frank MDS. The molecular heterogeneity seen in MDS is highly complex and includes mutations of genes involved in splicing machinery, epigenetic regulation, differentiation, and cell signaling. Recent advances in the understanding of the molecular landscape of MDS have led to the development of improved risk assessment tools and novel therapies. Therapies targeting the underlying pathophysiology will hopefully further expand the armamentarium of MDS therapeutics, bringing us closer to a more individualized therapeutic approach based on the unique molecular profile of each patient and eventually improving the outcomes of patients with MDS. We review the epidemiology of MDS and the newly described MDS precursor conditions CH, CH of indeterminate potential, and CCUS. We then discuss central aspects of MDS pathophysiology and outline specific strategies targeting hallmarks of MDS pathophysiology, including ongoing clinical trials examining the efficacy of these therapeutic modalities.

show abstract

Section: Epidemiology Of Mds and Mds Precursor Conditionsmentioning

confidence: 99%

Epidemiology and Pathogenesis of Myelodysplastic Syndrome

Rotter,

Shimony,

Ling

et al. 2023

Cancer J

View full text Add to dashboard Cite

show abstract

“…DNA methylation is a methyltransferase mediated chemical process in which a methyl group is added to the C5 position of cytosine dinucleotides. CpG dinucleotides (CpG islands) are distributed invariably throughout the genome and are the prime spots of DNA methylation in the human genome [ 61 , 62 ]. In early embryonic stage, 60% of tissue-specific differentially methylated regions are methylated however, de-methylation occurs when embryonic cells transform into adult tissues [ 63 , 64 ].…”

Section: Genomic Approach In Nipsmentioning

confidence: 99%

Reappraisal of evolving methods in non-invasive prenatal screening: Discovery, biology and clinical utility

Rather¹,

Saha

2023

Heliyon

View full text Add to dashboard Cite

“…DNMT1 is a major protein in the hypermethylation of cancer cells [225,226]. In different cancers, the degree of poly(ADP-ribosyl)ation of PARP1 varies; it also depends on the role of the related regulatory protein known as PARG1 that reverses the PARP1 function by removing poly(ADP)ribose moieties from target proteins [227][228][229].…”

Section: Perspective and Conclusionmentioning

confidence: 99%

DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1

Srivastava

Lodhi

2022

Biomolecules

View full text Add to dashboard Cite

Mammalian genomic DNA methylation represents a key epigenetic modification and its dynamic regulation that fine-tunes the gene expression of multiple pathways during development. It maintains the gene expression of one generation of cells; particularly, the mitotic inheritance of gene-expression patterns makes it the key governing mechanism of epigenetic change to the next generation of cells. Convincing evidence from recent discoveries suggests that the dynamic regulation of DNA methylation is accomplished by the enzymatic action of TET dioxygenase, which oxidizes the methyl group of cytosine and activates transcription. As a result of aberrant DNA modifications, genes are improperly activated or inhibited in the inappropriate cellular context, contributing to a plethora of inheritable diseases, including cancer. We outline recent advancements in understanding how DNA modifications contribute to tumor suppressor gene silencing or oncogenic-gene stimulation, as well as dysregulation of DNA methylation in cancer progression. In addition, we emphasize the function of PARP1 enzymatic activity or inhibition in the maintenance of DNA methylation dysregulation. In the context of cancer remediation, the impact of DNA methylation and PARP1 pharmacological inhibitors, and their relevance as a combination therapy are highlighted.

show abstract

DNA methylation: a saga of genome maintenance in hematological perspective

Cited by 18 publications

References 92 publications

Epidemiology and Pathogenesis of Myelodysplastic Syndrome

Epidemiology and Pathogenesis of Myelodysplastic Syndrome

Reappraisal of evolving methods in non-invasive prenatal screening: Discovery, biology and clinical utility

DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1

Contact Info

Product

Resources

About