Mutation Research-Reviews in Mutation Research最新文献

{"title":"Methodologies for the detection and sequencing of the epigenetic-like oxidative DNA modification, 8-oxo-7,8-dihydroguanine","authors":"Weiheng Kong ,&nbsp;Yingqi Zhao ,&nbsp;Xiaoxia Dai ,&nbsp;Changjun You","doi":"10.1016/j.mrrev.2024.108516","DOIUrl":"10.1016/j.mrrev.2024.108516","url":null,"abstract":"<div><div>The human genome is constantly threatened by endogenous and environmental DNA damaging agents that can induce a variety of chemically modified DNA lesions including 8-oxo-7,8-dihydroguanine (OG). Increasing evidence has indicated that OG is not only a biomarker for oxidative DNA damage but also a novel epigenetic-like modification involved in regulation of gene expression in mammalian cells. Here we summarize the recent progress in OG research focusing on the following points: (i) the mechanism of OG production in organisms and its biological consequences in cells, (ii) the accurate identification of OG in low-abundance genomes and complex biological backgrounds, (iii) the development of OG sequencing methods. These studies will be helpful for further understanding of the molecular mechanisms of OG-induced mutagenesis and its potential roles in human development and diseases such as cancer.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"794 ","pages":"Article 108516"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Objectives and achievements of the HUMN project on its 26th anniversary","authors":"Michael Fenech ,&nbsp;Nina Holland ,&nbsp;Errol Zeiger ,&nbsp;Peter Wushou Chang ,&nbsp;Micheline Kirsch-Volders ,&nbsp;Claudia Bolognesi ,&nbsp;Helga Stopper ,&nbsp;Lisbeth E. Knudsen ,&nbsp;Siegfried Knasmueller ,&nbsp;Armen Nersesyan ,&nbsp;Philip Thomas ,&nbsp;Varinderpal Dhillon ,&nbsp;Permal Deo ,&nbsp;Bernhard Franzke ,&nbsp;Maria-Grazia Andreassi ,&nbsp;Blanca Laffon ,&nbsp;Karl-Heinz Wagner ,&nbsp;Hannu Norppa ,&nbsp;Juliana da Silva ,&nbsp;Emanuela V. Volpi ,&nbsp;Stefano Bonassi","doi":"10.1016/j.mrrev.2024.108511","DOIUrl":"10.1016/j.mrrev.2024.108511","url":null,"abstract":"<div><p>Micronuclei (MN) are a nuclear abnormality that occurs when chromosome fragments or whole chromosomes are not properly segregated during mitosis and consequently are excluded from the main nuclei and wrapped within nuclear membrane to form small nuclei. This maldistribution of genetic material leads to abnormal cellular genomes which may increase risk of developmental defects, cancers, and accelerated aging. Despite the potential importance of MN as biomarkers of genotoxicity, very little was known about the optimal way to measure MN in humans, the normal ranges of values of MN in healthy humans and the prospective association of MN with developmental and degenerative diseases prior to the 1980’s. In the early 1980’s two important methods to measure MN in humans were developed namely, the cytokinesis-block MN (CBMN) assay using peripheral blood lymphocytes and the Buccal MN assay that measures MN in epithelial cells from the oral mucosa. These discoveries greatly increased interest to use MN assays in human studies. In 1997 the Human Micronucleus (HUMN) project was founded to initiate an international collaboration to (i) harmonise and standardise the techniques used to perform the lymphocyte CBMN assay and the Buccal MN assay; (ii) establish and collate databases of MN frequency in human populations world-wide which also captured demographic, lifestyle and environmental genotoxin exposure data and (iii) use these data to identify the most important variables affecting MN frequency and to also determine whether MN predict disease risk. In this paper we briefly describe the achievements of the HUMN project during the period from the date of its foundation on 9th September 1997 until its 26th Anniversary in 2023, which included more than 200 publications and 23 workshops world-wide.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"794 ","pages":"Article 108511"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574224000243/pdfft?md5=fd871687966df5756a12b1b7573a635c&pid=1-s2.0-S1383574224000243-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations on the scoring of telomere aberrations in vertebrate cells detected by telomere or telomere plus centromere PNA-FISH","authors":"Alejandro D. Bolzán","doi":"10.1016/j.mrrev.2024.108507","DOIUrl":"10.1016/j.mrrev.2024.108507","url":null,"abstract":"<div><p>Given that telomeres play a fundamental role in maintaining genomic stability, the study of the chromosomal aberrations involving telomeric sequences is a topic of considerable research interest. In recent years, the scoring of these types of aberrations has been used in vertebrate cells, particularly human cells, to evaluate the effects of genotoxic agents on telomeres and the involvement of telomeric sequences on chromosomal aberrations. Currently, chromosomal aberrations involving telomeric sequences are evaluated in peripheral blood lymphocytes or immortalized cell lines, using telomere or telomere plus centromere fluorescence <em>in situ</em> hybridization (FISH) with Peptide Nucleic Acid (PNA) probes (PNA-FISH). The telomere PNA probe is more efficient in the detection of telomeric sequences than conventional FISH with a telomere DNA probe. In addition, the intensity of the telomeric PNA-FISH probe signal is directly correlated with the number of telomeric repeats. Therefore, use of this type of probe can identify chromosomal aberrations involving telomeres as well as determine the telomere length of the sample. There are several mistakes and inconsistencies in the literature regarding the identification of telomere aberrations, which prevent accurate scoring and data comparison between different publications concerning these types of aberrations. The aim of this review is to clarify these issues, and provide proper terminology and criteria for the identification, scoring, and analysis of telomere aberrations.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"794 ","pages":"Article 108507"},"PeriodicalIF":5.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal tract exposure to particles and DNA damage in animals: A review of studies before, during and after the peak of nanotoxicology","authors":"Peter Møller,&nbsp;Martin Roursgaard","doi":"10.1016/j.mrrev.2024.108491","DOIUrl":"10.1016/j.mrrev.2024.108491","url":null,"abstract":"<div><p>Humans ingest particles and fibers on daily basis. Non-digestible carbohydrates are beneficial to health and food additives are considered safe. However, titanium dioxide (E171) has been banned in the European Union because the European Food Safety Authority no longer considers it non-genotoxic. Ingestion of microplastics and nanoplastics are novel exposures; their potential hazardous effects to humans have been under the radar for many years. In this review, we have assessed the association between oral exposure to man-made particles/fibers and genotoxicity in gastrointestinal tract cells and secondary tissues. We identified a total of 137 studies on oral exposure to particles and fibers. This was reduced to 49 papers with sufficient quality and relevance, including exposures to asbestos, diesel exhaust particles, titanium dioxide, silver nanoparticles, zinc oxide, synthetic amorphous silica and certain other nanomaterials. Nineteen studies show positive results, 25 studies show null results, and 5 papers show equivocal results on genotoxicity. Recent studies seem to show null effects, whereas there is a higher proportion of positive genotoxicity results in early studies. Genotoxic effects seem to cluster in studies on diesel exhaust particles and titanium dioxide, whereas studies on silver nanoparticles, zinc oxide and synthetic amorphous silica seem to show mainly null effects. The most widely used genotoxic tests are the alkaline comet assay and micronucleus assay. There are relatively few results on genotoxicity using reliable measurements of oxidatively damaged DNA, DNA double strand breaks (γH2AX assay) and mutations. In general, evidence suggest that oral exposure to particles and fibers is associated with genotoxicity in animals.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108491"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574224000048/pdfft?md5=a58fdddbc0306c51b95b59e3a6e291cf&pid=1-s2.0-S1383574224000048-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into the role of ion channels in cellular DNA damage response","authors":"Kamila Maliszewska-Olejniczak,&nbsp;Piotr Bednarczyk","doi":"10.1016/j.mrrev.2024.108488","DOIUrl":"10.1016/j.mrrev.2024.108488","url":null,"abstract":"<div><p>The DNA damage response (DDR) is a complex and highly regulated cellular process that detects and repairs DNA damage. The integrity of the DNA molecule is crucial for the proper functioning and survival of cells, as DNA damage can lead to mutations, genomic instability, and various diseases, including cancer. The DDR safeguards the genome by coordinating a series of signaling events and repair mechanisms to maintain genomic stability and prevent the propagation of damaged DNA to daughter cells. The study of an ion channels in the context of DDR is a promising avenue in biomedical research. Lately, it has been reported that the movement of ions through channels plays a crucial role in various physiological processes, including nerve signaling, muscle contraction, cell signaling, and maintaining cell membrane potential. Knowledge regarding the involvement of ion channels in the DDR could support refinement of our approach to several pathologies, mainly cancer, and perhaps lead to innovative therapies. In this review, we focused on the ion channel's possible role in the DDR. We present an analysis of the involvement of ion channels in DDR, their role in DNA repair mechanisms, and cellular outcomes. By addressing these areas, we aim to provide a comprehensive perspective on ion channels in the DDR and potentially guide future research in this field. It is worth noting that the interplay between ion channels and the cellular DDR is complex and multifaceted. More research is needed to fully understand the underlying mechanisms and potential therapeutic implications of these interactions.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108488"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574224000012/pdfft?md5=4273466af8ee37ae24201aecf24cd5ae&pid=1-s2.0-S1383574224000012-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Super-enhancers: Implications in gastric cancer","authors":"Yizhou Huang ,&nbsp;Yanfei Huo ,&nbsp;Linying Huang ,&nbsp;Long Zhang ,&nbsp;Yanxiu Zheng ,&nbsp;Nasha Zhang ,&nbsp;Ming Yang","doi":"10.1016/j.mrrev.2024.108489","DOIUrl":"https://doi.org/10.1016/j.mrrev.2024.108489","url":null,"abstract":"<div><p>Gastric cancer (GC) is the fifth most prevalent malignancy and the third leading cause of cancer-related mortality globally. Despite intensive efforts to enhance the efficiencies of various therapeutics (chemotherapy, surgical interventions, molecular-targeted therapies, immunotherapies), the prognosis for patients with GC remains poor. This might be predominantly due to the limited understanding of the complicated etiology of GC. Importantly, epigenetic modifications and alterations are crucial during GC development. Super-enhancers (SEs) are a large cluster of adjacent enhancers that greatly activate transcription. SEs sustain cell-specific identity by enhancing the transcription of specific oncogenes. In this review, we systematically summarize how SEs are involved in GC development, including the SE landscape in GC, the SE target genes in GC, and the interventions related to SE functions for treating GC.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108489"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria act as a key regulatory factor in cancer progression: Current concepts on mutations, mitochondrial dynamics, and therapeutic approach","authors":"Sraddhya Roy ,&nbsp;Ananya Das ,&nbsp;Aparajita Bairagi ,&nbsp;Debangshi Das ,&nbsp;Ashna Jha ,&nbsp;Amit Kumar Srivastava ,&nbsp;Nabanita Chatterjee","doi":"10.1016/j.mrrev.2024.108490","DOIUrl":"10.1016/j.mrrev.2024.108490","url":null,"abstract":"<div><p>The diversified impacts of mitochondrial function vs. dysfunction have been observed in almost all disease conditions including cancers. Mitochondria play crucial roles in cellular homeostasis and integrity, however, mitochondrial dysfunctions influenced by alterations in the mtDNA can disrupt cellular balance. Many external stimuli or cellular defects that cause cellular integrity abnormalities, also impact mitochondrial functions. Imbalances in mitochondrial activity can initiate and lead to accumulations of genetic mutations and can promote the processes of tumorigenesis, progression, and survival. This comprehensive review summarizes epigenetic and genetic alterations that affect the functionality of the mitochondria, with considerations of cellular metabolism, and as influenced by ethnicity. We have also reviewed recent insights regarding mitochondrial dynamics, miRNAs, exosomes that play pivotal roles in cancer promotion, and the impact of mitochondrial dynamics on immune cell mechanisms. The review also summarizes recent therapeutic approaches targeting mitochondria in anti-cancer treatment strategies.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108490"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating functional genomics into the pathology-supported genetic testing framework implemented in South Africa: A future view of precision medicine for breast carcinomas","authors":"Claudia Christowitz ,&nbsp;Daniel W. Olivier ,&nbsp;Johann W. Schneider ,&nbsp;Maritha J. Kotze ,&nbsp;Anna-Mart Engelbrecht","doi":"10.1016/j.mrrev.2024.108492","DOIUrl":"https://doi.org/10.1016/j.mrrev.2024.108492","url":null,"abstract":"<div><p>A pathology-supported genetic testing (PSGT) framework was established in South Africa to improve access to precision medicine for patients with breast carcinomas. Nevertheless, the frequent identification of variants of uncertain significance (VUSs) with the use of genome-scale next-generation sequencing has created a bottleneck in the return of results to patients. This review highlights the importance of incorporating functional genomics into the PSGT framework as a proposed initiative. Here, we explore various model systems and experimental methods available for conducting functional studies in South Africa to enhance both variant classification and clinical interpretation. We emphasize the distinct advantages of using <em>in vitro</em>, <em>in vivo</em>, and translational <em>ex vivo</em> models to improve the effectiveness of precision oncology. Moreover, we highlight the relevance of methodologies such as protein modelling and structural bioinformatics, multi-omics, metabolic activity assays, flow cytometry, cell migration and invasion assays, tube-formation assays, multiplex assays of variant effect, and database mining and machine learning models. The selection of the appropriate experimental approach largely depends on the molecular mechanism of the gene under investigation and the predicted functional effect of the VUS. However, before making final decisions regarding the pathogenicity of VUSs, it is essential to assess the functional evidence and clinical outcomes under current variant interpretation guidelines. The inclusion of a functional genomics infrastructure within the PSGT framework will significantly advance the reclassification of VUSs and enhance the precision medicine pipeline for patients with breast carcinomas in South Africa.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108492"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S138357422400005X/pdfft?md5=aa777804167f7a1c16e902b565a644ca&pid=1-s2.0-S138357422400005X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of genetic and epigenetic GNAS alterations in the development of early-onset obesity","authors":"Alaa Abbas ,&nbsp;Ayat S Hammad ,&nbsp;Mashael Al-Shafai","doi":"10.1016/j.mrrev.2023.108487","DOIUrl":"10.1016/j.mrrev.2023.108487","url":null,"abstract":"<div><h3>Background</h3><p><em>GNAS</em> (guanine nucleotide-binding protein, alpha stimulating) is an imprinted gene that encodes G_sα, the α subunit of the heterotrimeric stimulatory G protein. This subunit mediates the signalling of a diverse array of G protein-coupled receptors (GPCRs), including the melanocortin 4 receptor (MC4R) that serves a pivotal role in regulating food intake, energy homoeostasis, and body weight. Genetic or epigenetic alterations in <em>GNAS</em> are known to cause pseudohypoparathyroidism in its different subtypes and have been recently associated with isolated, early-onset, severe obesity. Given the diverse biological functions that G_sα serves, multiple molecular mechanisms involving various GPCRs, such as MC4R, β₂- and β₃-adrenoceptors, and corticotropin-releasing hormone receptor, have been implicated in the pathophysiology of severe, early-onset obesity that results from genetic or epigenetic <em>GNAS</em> changes.</p></div><div><h3>Scope of review</h3><p>This review examines the structure and function of <em>GNAS</em> and provides an overview of the disorders that are caused by defects in this gene and may feature early-onset obesity. Moreover, it elucidates the potential molecular mechanisms underlying G_sα deficiency-induced early-onset obesity, highlighting some of their implications for the diagnosis, management, and treatment of this complex condition.</p></div><div><h3>Major conclusions</h3><p>G_sα deficiency is an underappreciated cause of early-onset, severe obesity. Therefore, screening children with unexplained, severe obesity for <em>GNAS</em> defects is recommended, to enhance the molecular diagnosis and management of this condition.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108487"},"PeriodicalIF":5.3,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574223000352/pdfft?md5=090d4b148a016ca8a32bd7dec45a574d&pid=1-s2.0-S1383574223000352-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital neutropenia: From lab bench to clinic bedside and back","authors":"Weronika Dobrewa,&nbsp;Marta Bielska,&nbsp;Katarzyna Bąbol-Pokora,&nbsp;Szymon Janczar,&nbsp;Wojciech Młynarski","doi":"10.1016/j.mrrev.2023.108476","DOIUrl":"10.1016/j.mrrev.2023.108476","url":null,"abstract":"<div><p>Neutropenia is a hematological condition characterized by a decrease in absolute neutrophil count (ANC) in peripheral blood, typically classified in adults as mild (1–1.5 × 10⁹/L), moderate (0.5–1 × 10⁹/L), or severe (&lt; 0.5 × 10⁹/L). It can be categorized into two types: congenital and acquired. Congenital severe chronic neutropenia (SCN) arises from mutations in various genes, with different inheritance patterns, including autosomal recessive, autosomal dominant, and X-linked forms, often linked to mitochondrial diseases. The most common genetic cause is alterations in the <em>ELANE</em> gene. Some cases exist as non-syndromic neutropenia within the SCN spectrum, where genetic origins remain unidentified. The clinical consequences of congenital neutropenia depend on granulocyte levels and dysfunction. Infants with this condition often experience recurrent bacterial infections, with approximately half facing severe infections within their first six months of life. These infections commonly affect the respiratory system, digestive tract, and skin, resulting in symptoms like fever, abscesses, and even sepsis. The severity of these symptoms varies, and the specific organs and systems affected depend on the genetic defect. Congenital neutropenia elevates the risk of developing acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), particularly with certain genetic variants. SCN patients may acquire <em>CSF3R</em> and <em>RUNX1</em> mutations, which can predict the development of leukemia. It is important to note that high-dose granulocyte colony-stimulating factor (G-CSF) treatment may have the potential to promote leukemogenesis. Treatment for neutropenia involves antibiotics, drugs that boost neutrophil production, or bone marrow transplants. Immediate treatment is essential due to the heightened risk of severe infections. In severe congenital or cyclic neutropenia (CyN), the primary therapy is G-CSF, often combined with antibiotics. The G-CSF dosage is gradually increased to normalize neutrophil counts. Hematopoietic stem cell transplants are considered for non-responders or those at risk of AML/MDS. In cases of WHIM syndrome, CXCR4 inhibitors can be effective. Future treatments may involve gene editing and the use of the diabetes drug empagliflozin to alleviate neutropenia symptoms.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108476"},"PeriodicalIF":5.3,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574223000248/pdfft?md5=b700112fc36be06e1de57be90d4bfa4b&pid=1-s2.0-S1383574223000248-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}