Clonal hematopoiesis and its role in the development of hematological diseases

Introduction. The formation of blood cells in a healthy individual is ensured by polyclonal hematopoiesis. Recent studies have shown that with age, large clones with a common genetic marker are found in the peripheral blood, i. e. cells originating from a single progenitor cell. This phenomenon is called clonal hematopoiesis. In some cases, people with clonal hematopoiesis develop hematological diseases.Aim — to describe and summarize current data on the relationship between clonal hematopoiesis and hematological diseases.Main findings. This review describes the history of detection of clonal hematopoiesis, its main properties, the most frequent mutations in hematopoietic clones associated with the risk of transformation into myelodysplastic syndrome, and acute myeloid leukemia. The meaning and possible pathogenesis of tumor transformation are discussed.

Pneumosclerotic changes in lung tissues as a sign of tumor transformation in workers of the main professions of coal mines

Introduction. The workers of coal mines are characterized by a high level of not only occupational diseases, but also oncological diseases. Modern knowledge in the field of studying pneumoconiosis contains many contradictions in the assessment of the pathogenetic mechanisms of lung damage, in particular, the morphogenesis of neoplastic changes in the respiratory system at the final stage of the disease with pronounced sclerotic changes. The study is devoted to the occurrence and development of tumor tissue in the miners working in the underground conditions. The task is to identify morphological trigger mechanisms for the development of oncological pathology in miners, relying on pathomorphological, immunohistochemical studies of the changes in the epithelial tissue of the airways, as well as various cellular communities of the bronchi, blood vessels of the lungs and lung tissue parenchyma using the example of epithelial-mesenchymal transformation under dust load. The purpose of this study was to determine the influence of the fibroplastic process on the development of oncological pathology in miners who worked in underground conditions. Materials and methods. Histological, immunohistochemical and morphometric studies of the respiratory system obtained during 50 autopsy works of a group of Kuzbass miners working in underground conditions was carried out. Cancer of various localization and histogenetic affiliation was previously diagnosed in 20 miners. The mucous membrane of the bronchi, respiratory tissue of the lungs, arteries and veins of the pulmonary circulation were studied. Immunohistochemical study was performed using monoclonal antibodies (marker of proliferation Ki-67, oncogene of proapoptotic activity Bcl-2, growth and neoangiogenesis factors, endothelial function factors CD-31 and CD-34, marker of epithelial tissue cytokeratin (cyt), muscle tissue markers - actin, desmin, vimentin, connective tissue markers - collagen, laminil, markers of intercellular interactions EMA, SMA). Results. Transformed fibroblasts, myofibroblasts are a cell population of dedifferentiated epithelial tissue with different expressions of nonspecific markers (desmin, actin, vimentin), capable of tumor transformation. Sclerotic tissue changes in pneumoconiosis are the areas of tumor transdifferentiation. Fibroblasts with an altered phenotype, namely myofibroblasts, are able to give rise to the growth of undifferentiated mesenchymal cell communities (tumor tissue), including atypical epithelial cells, adipocytes, chondrocytes and endotheliocytes. Conclusions. Epithelial-mesenchymal transformation can be a triggering mechanism for the development of tumor transformation from extensive fibrosed zones in miners with dust lung pathology. In this case, the main etiological factor of tumor progression is activated fibroplastic cells.

Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates

Cancer is one of the most complex and systemic diseases affecting the health of mankind, causing major deaths with a significant increase. This pathology is caused by several risk factors, of which genetic disturbances constitute the major elements, which not only initiate tumor transformation but also epigenetic disturbances which are linked to it and which can induce transcriptional instability. Indeed, the involvement of epigenetic disturbances in cancer has been the subject of correlations today, in addition to the use of drugs that operate specifically on different epigenetic pathways. Natural molecules, especially those isolated from medicinal plants, have shown anticancer effects linked to mechanisms of action. The objective of this review is to explore the anticancer effects of alkaloids, terpenoids, quinones, and isothiocyanates.

Autophagy Modulation by Viral Infections Influences Tumor Development

Autophagy is a self-degradative process important for balancing cellular homeostasis at critical times in development and/or in response to nutrient stress. This is particularly relevant in tumor model in which autophagy has been demonstrated to have an important impact on tumor behavior. In one hand, autophagy limits tumor transformation of precancerous cells in early stage, and in the other hand, it favors the survival, proliferation, metastasis, and resistance to antitumor therapies in more advanced tumors. This catabolic machinery can be induced by an important variety of extra- and intracellular stimuli. For instance, viral infection has often been associated to autophagic modulation, and the role of autophagy in virus replication differs according to the virus studied. In the context of tumor development, virus-modulated autophagy can have an important impact on tumor cells’ fate. Extensive analyses have shed light on the molecular and/or functional complex mechanisms by which virus-modulated autophagy influences precancerous or tumor cell development. This review includes an overview of discoveries describing the repercussions of an autophagy perturbation during viral infections on tumor behavior.

Role of the bone marrow microenvironment in tumor transformation of plasma cell dyscrasias

Despite significant progress in the understanding of the pathogenesis of paraproteinemic hemoblastoses, these diseases remain incurable. In their development, they go through the stage of paraproteinemias, benign diseases, characterized by the detection of monoclonal paraprotein in the blood serum and / or urine, presence of clonal plasma cells in the bone marrow or in extramedullary tissues. It remains unclear why some paraproteinemias progress to multiple myeloma or other lymphoid tumors and how malignant progression occurs. An important role in the progression is played by molecular and genetic mechanisms, cytokines. Nevertheless, little is known about how the bone marrow microenvironment influences disease progression. In this review, we made an attempt to summarize the most significant biological, clinical characteristics on the course of paraproteinemias and the role of changes in the bone marrow microenvironment that contribute to malignant transformation.

Autophagy in Viral Development and Progression of Cancer

Autophagy is a complex degradative process by which eukaryotic cells capture cytoplasmic components for subsequent degradation through lysosomal hydrolases. Although this catabolic process can be triggered by a great variety of stimuli, action in cells varies according to cellular context. Autophagy has been previously linked to disease development modulation, including cancer. Autophagy helps suppress cancer cell advancement in tumor transformation early stages, while promoting proliferation and metastasis in advanced settings. Oncoviruses are a particular type of virus that directly contribute to cell transformation and tumor development. Extensive molecular studies have revealed complex ways in which autophagy can suppress or improve oncovirus fitness while still regulating viral replication and determining host cell fate. This review includes recent advances in autophagic cellular function and emphasizes its antagonistic role in cancer cells.

Comparison of the Allelic Alterations between InDel and STR Markers in Tumoral Tissues Used for Forensic Purposes

Background and objectives: Over the last two decades, human DNA identification and kinship tests have been conducted mainly through the analysis of short tandem repeats (STRs). However, other types of markers, such as insertion/deletion polymorphisms (InDels), may be required when DNA is highly degraded. In forensic genetics, tumor samples may sometimes be used in some cases of human DNA identification and in paternity tests. Nevertheless, tumor genomic instability related to forensic DNA markers should be considered in forensic analyses since it can compromise genotype attribution. Therefore, it is useful to know what impact tumor transformation may have on the forensic interpretation of the results obtained from the analysis of these polymorphisms. Materials and Methods: The aim of this study was to investigate the genomic instability of InDels and STRs through the analysis of 55 markers in healthy tissue and tumor samples (hepatic, gastric, breast, and colorectal cancer) in 66 patients. The evaluation of genomic instability was performed comparing InDel and STR genotypes of tumor samples with those of their healthy counterparts. Results: With regard to STRs, colorectal cancer was found to be the tumor type affected by the highest number of mutations, whereas in the case of InDels the amount of genetic mutations turned out to be independent of the tumor type. However, the phenomena of genomic instability, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), seem to affect InDels more than STRs hampering genotype attribution. Conclusion: We suggest that the use of STRs rather than InDels could be more suitable in forensic genotyping analyses given that InDels seem to be more affected than STRs by mutation events capable of compromising genotype attribution.

Regulation of the thioredoxin-dependent system as an element of pharmacotherapy in redox-impaired diseases

The action of many exogenous factors as well as disturbed metabolic processes of cells contribute to the increased production of oxidants, which leads to redox imbalance and, as a consequence, metabolic changes, including death or tumor transformation of cells. However, each cell is equipped with antioxidants to prevent this type of situation.One of the antioxidant systems functioning in cells is the thioredoxin dependent system, which includes thioredoxin (Trx), thioredoxin reductase (TrxR) and thioredoxin peroxidase (TPx), which have the ability to reduce oxidized forms of cell components at the expense of nicotinamidoadenine dinucleotide phosphate (NADPH). This effect results from the spatial structure of Trx and TrxR, which allows the formation of an intramolecular disulfide bridge within the thioredoxin molecule and two intermolecular selenesulfide bridges within the thioredoxin reductase dimer. Another, equally important function of the thioredoxin-dependent system is to regulate the expression of many proteins through factors such as NFκB transcription factor and apoptosis regulating kinase (ASK-1), which trigger cascades of metabolic transformations ultimately leading to cell proliferation or apoptosis. The increase in expression /activity of Trx-dependent system components is observed in the development of many cancers. Therefore, the search for selective thioredoxin or thioredoxin reductase inhibitors is currently one of the main research directions in cancer pharmacotherapy. It has been shown that many naturally occurring polyphenolic compounds of natural origin with antioxidant activity (e.g. quercetin or curcumin) inactivate the Trx-dependent system. At the same time, a number of synthetic compounds, including complex compounds, that are used in cancer therapy (e.g. cisplatin, auranofin, gadolinium motexafin) also inhibit the action of the thioredoxin system.

Cancer-testis antigen MAGE-C1/ CT7 in multiple myeloma: literature review

Group of tumor-associated antigens, which is normally expressed in placental cells and testicular germ cells, is called cancer-testis antigens. To date, more than 40 gene families have been identified that encode cancer-testis antigens, and their expression has been studied in many types of malignant diseases. It is assumed that the expression of cancer-testis antigens can contribute to the development of the tumor transformation process, including hematological diseases. Of particular interest in the pathogenesis of multiple myeloma is the MAGE-C1/CT7 antigen, the expression of which is most often detected in this case. According to data published by various authors, the expression of MAGEC1 in multiple myeloma can be considered as an additional marker of a poor disease prognosis, represent the effectiveness of chemotherapy approaches, and, possibly, be an earlier predictor of relapse or progression.

Trichoblastoma Complicating Jadassohn's Sebaceous Hamartoma

Jadassohn's Sebaceous Hamartoma (HSJ) is a complex congenital dysembryoplasia. The tumor transformation occurs in adulthood, often in a benign form.