Luspatercept: A New Tool for the Treatment of Anemia Related to β-Thalassemia, Myelodysplastic Syndromes and Primary Myelofibrosis.

Anemia is a common feature of both benign and malignant hematologic diseases. Beta-thalassemia (β-thalassemia) syndromes are a group of hereditary disorders characterized by ineffective erythropoiesis, due to a genetic deficiency in the synthesis of the beta chains of hemoglobin, often accompanied by severe anemia and the need for red blood cell (RBC) transfusions. Myelodysplastic syndromes (MDS) are characterized by cytopenia(s) and ineffective hematopoiesis, despite a hypercellular bone marrow.

Epialleles and epiallelic heterogeneity in hematological malignancies.

DNA methylation has a well-established role in the pathogenesis, prognosis, and response to treatment in all the spectra of hematological malignancies. However, most of the data reported involve average DNA methylation observed in a sample. The emergence of bisulfite sequencing methods such as enhanced reduced representation that permit analyze adjacent CpGs led to exciting findings.

Long non-coding RNAs and MYC association in hematological malignancies.

Long non-coding RNAs (lncRNAs) have an established role in cell biology. Among their functions is the regulation of hematopoiesis. They characterize the different stages of hematopoiesis in a more lineage-restricted expression pattern than coding mRNAs.

Enhancers and MYC interplay in hematopoiesis.

Transcription requires the fine interplay between enhancers and transcription factors. Enhancers are able to activate transcription of genes involved in normal cell biology, whereas aberrant enhancer activity leads to oncogenesis. MYC is a well-established proto-oncogene involved in half of human cancers amplifying the output of its targets.

Enhancer DNA methylation in acute myeloid leukemia and myelodysplastic syndromes.

DNA methylation (CpG methylation) exerts an important role in normal differentiation and proliferation of hematopoietic stem cells and their differentiated progeny, while it has also the ability to regulate myeloid versus lymphoid fate. Mutations of the epigenetic machinery are observed in hematological malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) resulting in hyper- or hypo-methylation affecting several different pathways. Enhancers are cis-regulatory elements which promote transcription activation and are characterized by histone marks including H3K27ac and H3K4me1/2.

The crosstalk between long non-coding RNAs and PI3K in cancer.

Long non-coding RNAs (lncRNAs) are able to positively or negatively regulate other genes expression in cis or in trans. Their effect can be achieved through RNA-protein, RNA-DNA, or RNA-RNA interactions. They can recruit transcription factors and act as scaffolds or guides for chromatin-modifying enzymes.

On the potential role of DNMT1 in acute myeloid leukemia and myelodysplastic syndromes: not another mutated epigenetic driver.

DNA methylation is the most common epigenetic modification in the mammalian genome. DNA methylation is governed by the DNA methyltransferases mainly DNMT1, DNMT3A, and DNMT3B. DNMT1 methylates hemimethylated DNA ensuring accurate DNA methylation maintenance.

Imprinted genes in myeloid lineage commitment in normal and malignant hematopoiesis.

Genomic imprinting is characterized by the parent-of-origin monoallelic expression of several diploid genes because of epigenetic regulation. Imprinted genes (IGs) are key factors in development, supporting the ability of a genotype to produce phenotypes in response to environmental stimuli. IGs are highly expressed during prenatal stages but are downregulated after birth.

DLK1-DIO3 imprinted cluster in induced pluripotency: landscape in the mist.

DLK1-DIO3 represents an imprinted cluster which genes are involved in physiological cell biology as early as the stem cell level and in the pathogenesis of several diseases. Transcription factor-mediated induced pluripotent cells (iPSCs) are considered an unlimited source of patient-specific hematopoietic stem cells for clinical application in patient-tailored regenerative medicine. However, to date there is no marker established able to distinguish embryonic stem cell-equivalent iPSCs or safe human iPSCs.

The role of sex and biochemical markers of inflammation in left ventricular remodelling, before and after surgery, in elderly patients with aortic valve stenosis.

Introduction: The aim of this study was to determine whether sex and biochemical markers of inflammation have a role in left ventricular (LV) remodelling after aortic valve replacement in elderly patients with aortic valve stenosis.

Methods: We studied 52 elderly patients with aortic valve stenosis (32 men, mean age 65 +/- 11 years and 20 women, mean age 68 +/- 9 years). Body surface area did not differ between men and women (1.

Transient complete atrioventricular block associated with herb intake.

We report a case of transient complete atrioventricular block in a 38-year-old man, after intake of a mixture of herbs, intended to aid cigarette smoking cessation. Since all other causes of conduction disturbances were excluded, a side-effect of the herbal remedy was identified as the most likely diagnosis. Given that most patients are unaware of the potential risks of the intake of various herbs, we would urge that their usage be regulated.