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Recent Clinical Update of Acute Myeloid Leukemia: Focus on Epigenetic Therapies.

Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN

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… TETonic Shift: Biological Roles of TET Proteins in DNA Demethylation and Transcription. Nat. Rev. Mol. Cel. Biol. 14, 341–356. 10.1038/nrm3589 Pillay N., Brady R. M., Dey M., Morgan R. D., Taylor S. S. (2021). …

Венецоклакс в сочетании с азаситидином в лечении вторичного миэлодипластического синдрома после нескольких миелом: доклад о деле и обзор литературы.

Мы провели ретроспективный анализ клинических данных пациента с миелодипластическим синдромом (MDS) вторичной и стабильной миеломой (MM), который лечился вместе с венетоклаксом и азаситидином в Пятом народном госпитале Ченду. Кроме того, мы изучили соответствующую литературу. Пациентка, 74-year-old Мужчина был первоначально диагностирован миеломой (IgA-__, DS IIIA, ISS III, R-ISS II) и получил очень хороший частичный ответ (VGPR) после последовательного лечения в рамках режимов BCTD, RVD и PVD, которые впоследствии получали алидомидную терапию. Несмотря на постоянную ремиссию, у пациента появи

As4S4 Exhibits Good Killing Effect on Multiple Myeloma Cells Via Repressing SOCS1 Methylation-Mediated JAK2/STAT3 Signaling Pathway.

ObjectiveThis study aimed to investigate the effect of tetra-arsenic tetra-sulfide on treating multiple myeloma and its potential regulation on suppressor of cytokine signaling 1 methylation-mediated Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway.MethodsTetra-arsenic tetra-sulfide with different concentrations were used to treat U266 cells, and cell viability was measured at 12, 24, and 48 hours with 0 μM tetra-arsenic tetra-sulfide treatment as control by Cell Counting Kit-8 assay. Suppressor of cytokine signaling 1 methylation and expression were determin

Fucoidan: An Update on Function, Role in Human Health and Applications.

Fucoidan is a polysaccharide bioactive compound, mainly from brown algae, characterized by multiple biological activities, including anti-inflammatory, anticoagulant, anticancer, antioxidant, antiviral, and cardioprotective properties. In addition, growing scientific evidence supports its epigenetic potential and ability to modulate autophagic mechanisms, two crucial aspects for the treatment and prevention of chronic diseases, such as cancer, inflammation, and aging. For this reason, Fucoidan is a promising candidate for a wide range of applications, both as a bioactive component of drug deli

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… In diabetic cognitive dysfunction epigenetic alterations, and in particular DNA demethylation, appear to be crucial for the development of the disease (Chen et al. 2024 ). … In the cerebral cortex of diabetic mouse models (MOD), due to DNA demethylation, the levels of 5‐hydroxymethylcytosine and 5‐formylcytosine are reduced (Chen et al. 2024 ). …

Epigenetics in myeloproliferative neoplasms.

The myeloproliferative neoplasms (MPNs) are a group of acquired clonal disorders where mutations drive proliferative disease resulting in increased blood counts and in some cases end-stage myelofibrosis. Epigenetic changes are the reversible modifications to DNA- and RNA-associated proteins that impact gene activity without changing the DNA sequence. This review summarizes mechanisms of epigenetic changes and the nucleosome. The drivers and epigenetic regulators in MPNs are outlined. In MPNs, distinct patterns of epigenetic dysregulation have been seen in chronic and in advanced phases. Methyl

RNA modifications in cancer.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise

Beyond regulations at DNA levels: A review of epigenetic therapeutics targeting cancer stem cells.

In the past few years, the paramount role of cancer stem cells (CSCs), in terms of cancer initiation, proliferation, metastasis, invasion and chemoresistance, has been revealed by accumulating studies. However, this level of cellular plasticity cannot be entirely explained by genetic mutations. Research on epigenetic modifications as a complementary explanation for the properties of CSCs has been increasing over the past several years. Notably, therapeutic strategies are currently being developed in an effort to reverse aberrant epigenetic alterations using specific chemical inhibitors. In thi

The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.

The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransfe

NETs: organ-related epigenetic derangements and potential clinical applications.

High-throughput next-generation sequencing methods have recently provided a detailed picture of the genetic landscape of neuroendocrine tumors (NETs), revealing recurrent mutations of chromatin-remodeling genes and little-to-no pathogenetic role for oncogenes commonly mutated in cancer. Concurrently, multiple epigenetic modifications have been described across the whole spectrum of NETs, and their putative function as tumorigenic drivers has been envisaged. As result, it is still unclear whether or not NETs are epigenetically-driven, rather than genetically-induced malignancies. Although the N

Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.

The dynamic changes in chromatin conformation alter the organization and structure of the genome and further regulate gene transcription. Basically, the chromatin structure is controlled by reversible, enzyme-catalyzed covalent modifications to chromatin components and by noncovalent ATP-dependent modifications via chromatin remodeling complexes, including switch/sucrose nonfermentable (SWI/SNF), inositol-requiring 80 (INO80), imitation switch (ISWI) and chromodomain-helicase DNA-binding protein (CHD) complexes. Recent studies have shown that chromatin remodeling is essential in different stag

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… DNA demethylation is realized by either an active pathway involving the dioxygenases called ten-eleven translocation (TET) proteins, including TET1, TET2 and TET3, to remove the methyl group from 5mC, or a passive pathway by lack of maintenance methylation (mediated by DNMT1) during cell divisions [ …

Сопутствующая реанимация острого миелоида лейкемии, связанного с терапией, и ИгГ-МГС во время устного децитабина-седазуридина: доклад по делу.

Фон и клиническая значимость: связь между острой миэлоидной лейкемией (АМЛ) и моноклонной гаммопатией неопределенного значения (МГУС) является редкой и, вероятно, случайной из-за аналогичной эпидемиологии этих двух кровеносных расстройств у пожилых пациентов, которые не имеют права на интенсивную химиотерапию или агрессивное лечение, поскольку они могут быть чрезмерно миэлоспрессивными. Такие методы лечения включают в себя те, которые содержат венетоклакс, легкую для использования разнородную форму децитабина-цедазуридина (DEC-C), которая в настоящее время доступна и утверждена для целей борьб

Investigating the Interplay between Myeloma Cells and Bone Marrow Stromal Cells in the Development of Drug Resistance: Dissecting the Role of Epigenetic Modifications.

Multiple Myeloma (MM) is a malignancy of plasma cells infiltrating the bone marrow (BM). Many studies have demonstrated the crucial involvement of bone marrow stromal cells in MM progression and drug resistance. Together with the BM microenvironment (BMME), epigenetics also plays a crucial role in MM development. A variety of epigenetic regulators, including histone acetyltransferases (HATs), histone methyltransferases (HMTs) and lysine demethylases (KDMs), are altered in MM, contributing to the disease progression and prognosis. In addition to histone modifications, DNA methylation also plays

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance.

Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15-20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed. Due to high proliferative rates and also the limited oxygen and nutrient diffusion in tumors, the development of hypoxic regions and consequent activation of hypoxia-inducible factors (HIFs) are a common characteristic of solid tumo

Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabo

Interpreting clinical assays for histone deacetylase inhibitors.

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development steps. When "imprinted" early by the environment, epigenetic changes influence the organism at an early stage and can be transmitted to the progeny. Together with DNA sequence alterations, DNA aberrant cytosine methylation and microRNA deregulat

The DNA methylation landscape of multiple myeloma shows extensive inter- and intrapatient heterogeneity that fuels transcriptomic variability.

BackgroundCancer evolution depends on epigenetic and genetic diversity. Historically, in multiple myeloma (MM), subclonal diversity and tumor evolution have been investigated mostly from a genetic perspective.MethodsHere, we performed an analysis of 42 MM samples from 21 patients by using enhanced reduced representation bisulfite sequencing (eRRBS). We combined several metrics of epigenetic heterogeneity to analyze DNA methylation heterogeneity in MM patients.ResultsWe show that MM is characterized by the continuous accumulation of stochastic methylation at the promoters of development-related

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… This is likely to be due to the multiple rounds of mitotic division coupled with DNA demethylation that plasmablasts and plasma cells undergo during differentiation [ 54 , 55 ]. …

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science.

Traditional Chinese medicine (TCM) has been practiced for thousands of years and at the present time is widely accepted as an alternative treatment for cancer. In this review, we sought to summarize the molecular and cellular mechanisms underlying the chemopreventive and therapeutic activity of TCM, especially that of the Chinese herbal medicine-derived phytochemicals curcumin, resveratrol, and berberine. Numerous genes have been reported to be involved when using TCM treatments and so we have selectively highlighted the role of a number of oncogene and tumor suppressor genes in TCM therapy. I

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… As far as can be ascertained, investigations of the relationship between TCM and DNA demethylation are limited. Dioscin, a natural steroid saponin, has been identified in CHM. … demethylation. …

RNA N 6-Methyladenosine in Cancer Metastasis: Roles, Mechanisms, and Applications.

Cancer metastasis is a symptom of adverse prognosis, a prime origin of therapy failure, and a lethal challenge for cancer patients. N 6-methyladenosine (m6A), the most prevailing modification in messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) of higher eukaryotes, has attracted increasing attention. Growing studies have verified the pivotal roles of m6A methylation in controlling mRNAs and ncRNAs in diverse physiological processes. Remarkably, recent findings have showed that aberrant methylation of m6A-related RNAs could influence cancer metastasis. In this review, we illuminate how m6A m