Seminars in hematology最新文献

{"title":"Immune-driven clonal cell selection at the intersection among cancer, infections, autoimmunity and senescence","authors":"Simona Pagliuca ,&nbsp;Francesca Ferraro","doi":"10.1053/j.seminhematol.2024.01.002","DOIUrl":"10.1053/j.seminhematol.2024.01.002","url":null,"abstract":"<div><p>Immune surveillance mechanisms play a crucial role in maintaining lifelong immune homeostasis in response to pathologic stimuli and aberrant cell states. However, their persistence, especially in the context of chronic antigenic exposure, can create a fertile ground for immune evasion. These escaping cell phenotypes, harboring a variety of genomic and transcriptomic aberrances, chiefly in human leukocyte antigen (HLA) and antigen presentation machinery genes, may survive and proliferate, featuring a scenario of clonal cell expansion with immune failure characteristics. While well characterized in solid and, to some extent, hematological malignancies, little is known about their occurrence and significance in other disease contexts.</p><p>Historical literature highlights the role for escaping HLA-mediated recognition as a strategy adopted by virus to evade from the immune system, hinting at the potential for immune aberrant cell expansion in the context of chronic infections. Additionally, unmasked in idiopathic aplastic anemia as a mechanism able to rescue failing hematopoiesis, HLA clonal escape may operate in autoimmune disorders, particularly in tissues targeted by aberrant immune responses. Furthermore, senescent cell status emerging as immunogenic phenotypes stimulating T cell responses, may act as a bottleneck for the selection of such immune escaping clones, blurring the boundaries between neoplastic transformation, aging and inflammation. Here we provide a fresh overview and perspective on this immune-driven clonal cell expansion, linking pathophysiological features of neoplastic, autoimmune, infectious and senescence processes exposed to immune surveillance.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 22-34"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0037196324000015/pdfft?md5=735f93d1eb51fc06c833a2ce8eddfcac&pid=1-s2.0-S0037196324000015-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139500726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tower of babel of acronyms? The shadowlands of MGUS/MBL/CHIP/TCUS","authors":"Carlos Bravo-Perez ,&nbsp;Carmelo Gurnari","doi":"10.1053/j.seminhematol.2024.01.004","DOIUrl":"10.1053/j.seminhematol.2024.01.004","url":null,"abstract":"<div><p>With the advent of outperforming and massive laboratory tools, such as multiparameter flow cytometry and next-generation sequencing, hematopoietic cell clones with putative abnormalities for a variety of blood malignancies have been appreciated in otherwise healthy individuals. These conditions do not fulfill the criteria of their presumed cancer counterparts, and thus have been recognized as their precursor states. This is the case of monoclonal gammopathy of unknown significance (MGUS), the first blood premalignancy state described, preceding multiple myeloma (MM) or Waldenström macroglobulinemia (WM). However, in the last 2 decades, an increasing list of clonopathies has been recognized, including monoclonal B cell lymphocytosis (MBL), which antecedes chronic lymphocytic leukemia (CLL), clonal hematopoiesis of indeterminate potential (CHIP) for myeloid neoplasms (MN), and T-cell clones of uncertain significance (TCUS) for T-cell large chronic lymphocytic leukemia (LGLL). While for some of these entities diagnostic boundaries are precisely set, for others these are yet to be fully defined. Moreover, despite mostly considered of “uncertain significance,” they have not only appeared to predispose to malignancy, but also to be capable of provoking set of immunological and cardiovascular complications that may require specialized management. The clinical implications of the aberrant clones, together with the extensive knowledge generated on the pathogenetic events driving their evolution, raises the question whether earlier interventions may alter the natural history of the disease. Herein, we review this Tower of Babel of acronyms pinpointing diagnostic definitions, differential diagnosis, and the role of genomic profiling of these precursor states, as well as potential interventional strategies.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 43-50"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET2 mutation as prototypic clonal hematopoiesis lesion","authors":"Luca Guarnera ,&nbsp;Babal K. Jha","doi":"10.1053/j.seminhematol.2024.01.013","DOIUrl":"10.1053/j.seminhematol.2024.01.013","url":null,"abstract":"<div><p>Loss of function <em>TET2</em> mutation (<em>TET2^MT</em>) is one of the most frequently observed lesions in clonal hematopoiesis (CH). TET2 a member TET-dioxygenase family of enzymes that along with TET1 and TET3, progressively oxidize 5-methyl cytosine (mC) resulting in regulated demethylation of promoter, enhancer and silencer elements of the genome. This process is critical for efficient transcription that determine cell lineage fate, proliferation and survival and the maintenance of the genomic fidelity with aging of the organism. Partial or complete loss-of-function <em>TET2</em> mutations create regional and contextual DNA hypermethylation leading to gene silencing or activation that result in skewed myeloid differentiation and clonal expansion. In addition to myeloid skewing, loss of <em>TET2</em> creates differentiation block and provides proliferative advantage to hematopoietic stem and progenitor cells (HSPCs). <em>TET2^MT</em> is a prototypical lesion in CH, since the mutant clones dominate during stress hematopoiesis and often associates with evolution of myeloid malignancies. <em>TET2^MT</em> clones has unique privilege to create and persist in pro-inflammatory milieu. Despite extensive knowledge regarding biochemical mechanisms underlying distorted myeloid differentiation, and enhanced self-replication of <em>TET2^MT</em> HSPC, the mechanistic link of various pathogenesis associated with <em>TET2</em> loss in CHIP is less understood. Here we review the recent development in <em>TET2</em> biology and its probable mechanistic link in CH with aging and inflammation. We also explored the therapeutic strategies of targeting <em>TET2^MT</em> associated CHIP and the utility of targeting <em>TET2</em> in normal hematopoiesis and somatic cell reprograming. We explore the biochemical mechanisms and candidate therapies that emerged in last decade of research.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 51-60"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"outside front cover, PMS 8883 metallic AND 4/C","authors":"","doi":"10.1053/S0037-1963(24)00040-4","DOIUrl":"https://doi.org/10.1053/S0037-1963(24)00040-4","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Page CO1"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140296055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis in the setting of hematopoietic cell transplantation","authors":"Christopher J. Gibson ,&nbsp;R. Coleman Lindsley ,&nbsp;Lukasz P. Gondek","doi":"10.1053/j.seminhematol.2024.01.011","DOIUrl":"10.1053/j.seminhematol.2024.01.011","url":null,"abstract":"<div><p>Clonal hematopoiesis (CH) in autologous transplant recipients and allogeneic transplant donors has genetic features and clinical associations that are distinct from each other and from non-cancer populations. CH in the setting of autologous transplant is enriched for mutations in DNA damage response pathway genes and is associated with adverse outcomes, including an increased risk of therapy-related myeloid neoplasm and inferior overall survival. Studies of CH in allogeneic transplant donors have yielded conflicting results but have generally shown evidence of potentiated alloimmunity in recipients, with some studies showing an association with favorable recipient outcomes.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 9-15"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crossroads of cancer therapies and clonal hematopoiesis","authors":"Abhay Singh ,&nbsp;Suresh Balasubramanian","doi":"10.1053/j.seminhematol.2024.01.006","DOIUrl":"10.1053/j.seminhematol.2024.01.006","url":null,"abstract":"<div><p>The intricate interplay between Clonal Hematopoiesis (CH) and the repercussions of cancer therapies has garnered significant research focus in recent years. Previously perceived as an age-related phenomenon, CH is now closely linked to inflammation (“Inflammaging”) and cancer, impacting leukemogenesis, cancer progression, and treatment responses. This review explores the complex interplay between CH and diverse cancer therapies, including chemotherapy, targeted treatments, radiation, stem cell transplants, CAR-T cell therapy, and immunotherapy, like immune checkpoint inhibitors. Notably, knowledge about post-chemotherapy CH mutation/acquisition has evolved from a <em>de novo</em> incident to more of a clonal selection process. Chemotherapy and radiation exposure, whether therapeutic or environmental, increases CH risk, particularly in genes like <em>TP53</em> and <em>PPM1D</em>. Environmental toxins, especially in high-risk environments like post-disaster sites or space exploration, are associated with CH. CH affects clinical outcomes in stem cell transplant scenarios, including engraftment, survival, and t-MN development. The presence of CH also alters CAR-T cell therapy responses and impacts the efficacy and toxicity of immunotherapies. Furthermore, specific mutations like <em>DNMT3A</em> and <em>TET2</em> thrive under inflammatory stress, influencing therapy outcomes and justifying the ongoing tailored interventions in clinical trials. This review underscores the critical need to integrate CH analysis into personalized medicine, enhancing risk assessments and refining treatment strategies. As we progress, multidisciplinary collaboration and comprehensive studies are imperative. Understanding CH's impact, especially concerning genotoxic stressors, will inform screening, surveillance, and early detection strategies, decreasing the risk of therapy-related myeloid neoplasms and revolutionizing cancer treatment paradigms.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 16-21"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0037196324000076/pdfft?md5=9ebeaac0cb20f6a2472ddf443fbcff2c&pid=1-s2.0-S0037196324000076-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139500978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline predisposition for clonal hematopoiesis","authors":"Yasuo Kubota ,&nbsp;Aaron D. Viny","doi":"10.1053/j.seminhematol.2024.01.007","DOIUrl":"10.1053/j.seminhematol.2024.01.007","url":null,"abstract":"<div><p><span><span>Clonal hematopoiesis (CH) is an entity hallmarked by skewed hematopoiesis with persistent overrepresentation of cells from a common stem/progenitor lineage harboring single-nucleotide variants and/or insertions/deletions. CH is a common and age-related phenomenon that is associated with an increased risk of </span>hematological malignancies, cardiovascular disease, and all-cause mortality. While CH is a term of the hematological aspect, there exists a complex interaction with other organ systems, especially the cardiovascular system. The strongest factor in the development of CH is aging, however, other multiple factors also affect the development of CH including lifestyle-related factors and co-morbid diseases. In recent years, germline </span>genetic factors have been linked to CH risk. In this review, we synthesize what is currently known about how genetic variation affects the risk of CH, how this genetic architecture intersects with myeloid neoplasms, and future prospects for CH.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 61-67"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139475175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis and autoimmunity","authors":"Ashwin Kishtagari ,&nbsp;Robert W. Corty ,&nbsp;Valeria Visconte","doi":"10.1053/j.seminhematol.2024.01.012","DOIUrl":"10.1053/j.seminhematol.2024.01.012","url":null,"abstract":"<div><p>Clonal hematopoiesis (CH) has been associated with aging, occurring in about 10% of individuals aged &gt;70 years, and immune dysfunction. Aged hematopoietic stem and progenitor cells exhibit pathological changes in immune function and activation of inflammatory pathways. CH clones commonly harbor a loss of function mutation in <em>DNMT3A</em> or <em>TET2</em>, which causes increased expression of inflammatory signaling genes, a proposed mechanism connected to CH and the development of age-related diseases. Additionally, inflammation may stress the hematopoietic compartment, driving the expansion of mutant clones. While the epidemiologic overlap between CH, hematologic malignancies, and atherosclerotic cardiovascular diseases has been reported, the mechanisms linking these concepts are largely unknown and merit much further investigation. Here, we review studies highlighting the interplay between CH, inflamm-aging, the immune system, and the prevalence of CH in autoimmune diseases.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 3-8"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis","authors":"Jaroslaw P. Maciejewski (Editor)","doi":"10.1053/j.seminhematol.2024.01.014","DOIUrl":"10.1053/j.seminhematol.2024.01.014","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 1","pages":"Pages 1-2"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0037196324000143/pdfft?md5=424848dc0e4a0c07344787f75a54edb6&pid=1-s2.0-S0037196324000143-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology and etiology of diffuse large B-cell lymphoma","authors":"Sophia S. Wang","doi":"10.1053/j.seminhematol.2023.11.004","DOIUrl":"10.1053/j.seminhematol.2023.11.004","url":null,"abstract":"<div><div>As the most common non-Hodgkin lymphoma subtype, diffuse large B-cell lymphoma (DLBCL) incidence patterns generally parallel that for NHL overall. Globally, DLBCL accounts for a third of all NHLs, ranging between 20% and 50% by country. Based on United States (U.S.) cancer registry data, age-standardized incidence rate for DLBCL was 7.2 per 100,000. DLBCL incidence rises with age and is generally higher in males than females; in the U.S., incidence is highest among non-Hispanic whites (9.2/100,000). Like NHL incidence, DLBCL incidence rose in the first half of the 20th century but has largely plateaued. However, there is some evidence that incidence rates are rising in areas of historically low rates, such as Asia; there are also estimates for rising DLBCL incidence in the near future due to the changing demographics in developed countries whose aging population is growing. Established risk factors for DLBCL include those that result in severe immune deficiency such as HIV/AIDS, inherited immunodeficiency syndromes, and organ transplant recipients. Factors that lead to chronic immune dysregulations are also established risk factors, and include a number of autoimmune conditions (eg, Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis), viral infections (eg, HIV, KSHV/HHV8, HCV, EBV), and obesity. Family history of NHL/DLBCL, personal history of cancer, and multiple genetic susceptibility loci are also well-established risk factors for DLBCL. There is strong evidence for multiple environmental exposures in DLBCL etiology, including exposure to trichloroethylene, benzene, and pesticides and herbicides, with recent associations noted with glyphosate. There is also strong evidence for associations with other viruses, such as HBV. Recent estimates suggest that obesity accounts for nearly a quarter of DLBCLs that develop, but despite recent gains in the understanding of DLBCL etiology, the majority of disease remain unexplained. An understanding of the host and environmental contributions to disease etiology, and concerted efforts to expand our understanding to multiple race/ethnic groups, will be essential for constructing clinically relevant risk prediction models and develop effective strategies for disease prevention.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"60 5","pages":"Pages 255-266"},"PeriodicalIF":5.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138537283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}