The DNA methylation landscape of hematological malignancies: an update

Blecua, Pedro; Martinez-Verbo, Laura; Esteller, Manel

doi:10.1002/1878-0261.12744

Cited by 39 publications

(27 citation statements)

References 177 publications

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“…Mutations in the discussed epigenetic modulators frequently occur in other hematological diseases. Recurrent TET2 , DNMT3A , IDH1/2 mutations have been observed in patients with myeloproliferative neoplasms and other hematological malignancies, such as acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or myelodysplastic syndromes (MDS) [ 38 , 39 ]. Thus, two questions can be raised: are these point mutations prognostic in SM and do these mutations have an impact on the responsiveness of neoplastic MC to various targeted drugs.…”

Section: Epigenetic Changes In Mastocytosismentioning

confidence: 99%

Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis

Reszka

Jabłońska

Wieczorek

et al. 2021

IJMS

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Systemic mastocytosis (SM) is a hematologic neoplasm with abnormal accumulation of mast cells in various organ systems such as the bone marrow, other visceral organs and skin. So far, only little is known about epigenetic changes contributing to the pathogenesis of SM. In the current article, we provide an overview of epigenetic changes that may occur and be relevant to mastocytosis, including mutations in genes involved in epigenetic processes, such as TET2, DNMT3A and ASXL1, and global and gene-specific methylation patterns in neoplastic cells. Moreover, we discuss methylation-specific pathways and other epigenetic events that may trigger disease progression in mast cell neoplasms. Finally, we discuss epigenetic targets and the effects of epigenetic drugs, such as demethylating agents and BET-targeting drugs, on growth and viability of neoplastic mast cells. The definitive impact of these targets and the efficacy of epigenetic therapies in advanced SM need to be explored in future preclinical studies and clinical trials.

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Section: Epigenetic Changes In Mastocytosismentioning

confidence: 99%

Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis

Reszka

Jabłońska

Wieczorek

et al. 2021

IJMS

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“…The cfDNA levels of lymphocytes specific, hypomethylated cg17587997, which occur in the 5’UTR of FYN, are markedly increased and may be linked to pathogenesis. 24 Since epigenetic changes crucially contribute to hematological malignancies, 25 further analyses of relevant methylation sites have a great potential for monitoring disease burden and treatment response. Here we provide evidence that cfDNA can be used as a robust, non-invasive, and cost-efficient sample source for targeted sequencing approaches.…”

Section: Resultsmentioning

confidence: 99%

Physical activity specifically evokes release of cell-free DNA from granulocytes thereby affecting liquid biopsy

Neuberger

Sontag

Brahmer

et al. 2021

Preprint

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Cell-free DNA (cfDNA) methylation-based diagnostics is a promising approach in oncology and hematooncology. Exercise impacts immune homeostasis and leads to a rapid and marked increase of cfDNA levels in blood. Since the origin of cfDNA during exercise remains elusive, the implications for liquid biopsy are unknown. In this study, we identified the source of cfDNA in 10 healthy untrained individuals before, immediately after, and 30 min after exercise, and in 6 patients with myeloid neoplasms or acute leukemia under resting conditions. A pyrosequencing assay was used to analyze the methylation levels of four CpGs, representing DNA from granulocytes, lymphocytes, monocytes, and non-hematopoietic cells. After exercise, cfDNA was almost exclusively released from granulocytes, with cell type specific proportions increasing significantly from 54.1% to 90.2%. Exercise did not trigger the release of cfDNA from lymphocytes or other analyzed cell types, whereas a small amount of cfDNA was released from monocytes. Compared to healthy people, patients with hematological malignancies show significantly higher cfDNA levels at rest with 48.1 (19.1; 78) vs. 8.5 (8.2; 9.5) ng/ml, data expressed as median (25th; 75th percentiles), and considerably higher levels of lymphocyte specific hypomethylated cg17587997 (P<.001). Hence, exercise-induced cfDNA elevations can compromise diagnostic accuracy.

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“…Independent of histones, cytosine methylation is a repressive mark occurring on the DNA molecule. DNA methyltransferases (DNMTs) add methyl groups to cytosine bases [36] . Importantly, DNA methylation can only be indirectly removed by TET enzymes and subsequent DNA repair pathways, or by dilution through cell divisions [37].…”

Section: Epigenetic Modification Of Histone Proteins In B-nhlmentioning

confidence: 99%

Histone Modifications and Their Targeting in Lymphoid Malignancies

Fernández-Serrano¹,

Winkler²,

Santos³

et al. 2021

Preprint

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In a wide range of lymphoid neoplasms, the process of malignant transformation is associated to somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in non-Hodgkin B-cell lymphoma. Furthermore, we aim to present in close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have greatest potential to improve the prognosis of lymphoma patients.

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The DNA methylation landscape of hematological malignancies: an update

Cited by 39 publications

References 177 publications

Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis

Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis

Physical activity specifically evokes release of cell-free DNA from granulocytes thereby affecting liquid biopsy

Histone Modifications and Their Targeting in Lymphoid Malignancies

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