The ‘instructive model’ of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also link methylation of CpG islands to the methylation status of H3K4, where H3K4me3 is inversely correlated with DNA methylation. To provide insight into these conflicting findings, we generated DNA methylation profiles for acute myeloid leukemia samples from patients and leukemic cell lines and integrated them with publicly available ChIp‐seq data, containing H3K4me3 and H3K27me3 CpG island occupation in hESC, or hematopoietic stem or progenitor cells (hHSC/MPP). Hypermethylated CpG islands in AML samples displayed H3K27me3 enrichments in hESC and hHSC/MPP; however, ChIp analysis of specific hypermethylated CpG islands revealed a significant reduction in H3K4me3 signal with a concomitant increase in H3K4me0 levels as opposed to a nonsignificant increase in H3K27me3 marks. The integration of AML DNA methylation profiles with the ChIp‐seq data in hESC and hHSC/MPP also led to the identification of Iroquois homeobox 2 (IRX2) as a previously unknown factor promoting differentiation of leukemic cells. Our results indicate that in contrast to the ‘instructive model’, H3K4me3 levels are strongly associated with DNA methylation patterns in AML and have a role in the regulation of critical genes, such as the putative tumor suppressor IRX2.
Retinal dysfunction is the most common cause of vision loss in several retinal disorders. It has been estimated a great increase in these pathologies that are becoming more globally widespread and numerous over time, also supported by the life expectancy increment. Among different types of retinopathies, we can account some that share causes, symptoms, and treatment including diabetic retinopathy, age-related macular degeneration, glaucoma, and retinitis pigmentosa. Molecular changes, environmental factors, and genetic predisposition might be some of the main causes that drive retinal tissue to chronic inflammation and neurodegeneration in these retinopathies. The treatments available on the market contain compounds that efficiently ameliorate some of the important clinical features of these pathologies like stabilization of the intraocular pressure, reduction of eye inflammation, control of eye oxidative stress which are considered the major molecular mechanisms related to retinal dysfunction. Indeed, the most commonly used drugs are anti-inflammatories, such as corticosteroids, antioxidant, hypotonic molecules and natural neuroprotective compounds. Unfortunately, these drugs, which are fundamental to treating disease symptoms, are not capable to cure the pathologies and so they are not life-changing for patients. This review provided an overview of current treatments on the market, but more interestingly, wants to be a quick window on the new treatments that are now in clinical trials. Additionally, it has been here highlighted that the recent technical enhancement of the investigation methods to identify the various retinopathies causes might be used as a sort of “precise medicine” approach to tailor the identification of molecular pathways involved and potentially study a dedicated treatment for each patient. This approach includes the use of cutting-edge technologies like gene therapy and metabolomics.
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