Seminars in hematology最新文献_第2页

Implications for metabolic disturbances in myelodysplastic syndromes. 骨髓增生异常综合征代谢紊乱的影响。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-12-01 Epub Date: 2024-11-22 DOI: 10.1053/j.seminhematol.2024.11.004

Kathy L McGraw, Daniel R Larson

{"title":"Implications for metabolic disturbances in myelodysplastic syndromes.","authors":"Kathy L McGraw, Daniel R Larson","doi":"10.1053/j.seminhematol.2024.11.004","DOIUrl":"10.1053/j.seminhematol.2024.11.004","url":null,"abstract":"The Myelodysplastic Syndromes (MDS) are heterogeneous stem cell malignancies clinically characterized by bone marrow dysplasia, peripheral blood cytopenias, and a high risk for transformation to acute myeloid leukemia. In early stages of disease, differentiation defects and maturation blocks result in deficient hematopoiesis. In higher risk disease, unrestricted proliferation of immature blast cells leads to leukemogenesis. Disease pathogenesis can be attributed to many factors including chronic inflammation that is driven in part by commonly found somatic gene mutations (SGM) fostering expansion of malignant clones while suppressing normal hematopoiesis. Cellular metabolism that both directly and indirectly regulates hematopoietic stem cell (HSC) fate, is intimately connected to the immune system, is altered by MDS somatic gene mutations and is likely is a major contributor to disease pathophysiology. Despite this likely role in pathobiology, there is an underwhelming depth of literature on the subject and the precise metabolic dysregulations in these myeloid malignancies have yet to be fully delineated. In this review, we will provide a general overview of several major metabolic processes and how each directs HSC fate, provide a summary of metabolic studies in MDS, discuss how common SGM and inflammation influence metabolic pathways to drive bone marrow failure, and end with a discussion of standards of care and how these should be carefully considered in the context of metabolic dysregulation.","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":"470-478"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740416","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}

引用次数: 0

Understanding MDS stem cells: Advances and limitations. 了解 MDS 干细胞：进展与局限。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-12-01 Epub Date: 2024-09-28 DOI: 10.1053/j.seminhematol.2024.09.007

Sweta B Patel, Daniel R Moskop, Craig T Jordan, Eric M Pietras

引用次数: 0

Patient-reported outcomes in early phase trials for patients with myelodysplastic syndromes. 骨髓增生异常综合征患者早期试验中的患者报告结果。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-12-01 Epub Date: 2024-10-30 DOI: 10.1053/j.seminhematol.2024.10.010

Tito Mendoza, Amanda L King, Elizabeth Vera, Alain Mina, Kathy McGraw, Steven Pavletic, Terri S Armstrong

{"title":"Patient-reported outcomes in early phase trials for patients with myelodysplastic syndromes.","authors":"Tito Mendoza, Amanda L King, Elizabeth Vera, Alain Mina, Kathy McGraw, Steven Pavletic, Terri S Armstrong","doi":"10.1053/j.seminhematol.2024.10.010","DOIUrl":"10.1053/j.seminhematol.2024.10.010","url":null,"abstract":"Patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) experience a wide range of symptoms due both to their underlying disease and the effects of treatment. Designing early phase trials to explore effective therapies in these patients should not only examine anti-tumor activity, but also consider the effects of treatments on how patients feel and function. Assessing symptomatic toxicities associated with new therapies in early phase trials from the patient perspective is best measured using patient-reported outcomes (PROs) and offers valuable insight and complementary information to the traditional adverse event reporting in cancer clinical trials. This review describes PROs, highlights their importance in MDS drug development, and outlines the key psychometric properties and practical considerations that make PROs essential and desirable in evaluating the impact of new therapies. We will provide a general overview of PROs and follow with application of PROs in MDS/AML including strategies to be considered in early phase trials. Finally, we describe the creation of the Office of Patient-Centered Outcomes Research at the US National Institutes of Health which has developed a standardized PROs methodology for early phase trials conducted in the Center for Cancer Research at the US National Cancer Institute.","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":"457-464"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627558","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}

引用次数: 0

RNA splicing as a therapeutic target in myelodysplastic syndromes. 将 RNA 剪接作为骨髓增生异常综合征的治疗靶点。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-12-01 Epub Date: 2024-10-23 DOI: 10.1053/j.seminhematol.2024.10.005

Chun-Chih Tseng, Esther A Obeng

引用次数: 0

IF 5 3区医学

Seminars in hematology Pub Date : 2024-12-01 Epub Date: 2024-09-21 DOI: 10.1053/j.seminhematol.2024.09.004

Sangeetha Venugopal, Amy E DeZern

引用次数: 0

The potential promise of machine learning in myelodysplastic syndrome.

IF 5 3区医学

Seminars in hematology Pub Date : 2024-11-16 DOI: 10.1053/j.seminhematol.2024.11.002

Valeria Visconte, Jaroslaw P Maciejewski, Luca Guarnera

{"title":"The potential promise of machine learning in myelodysplastic syndrome.","authors":"Valeria Visconte, Jaroslaw P Maciejewski, Luca Guarnera","doi":"10.1053/j.seminhematol.2024.11.002","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2024.11.002","url":null,"abstract":"The introduction of artificial intelligence (AI), and in particular machine learning (ML), has revolutionized biomedical research at the clinical level, a trend that also includes hematologic malignancies and myeloid neoplasia (MN). ML encompasses a wide range of applications such as enhanced diagnostics, outcome predictions, decision trees and clustering. Despite several reports in recent years and the achievement of promising results, none of the ML-based pipelines have been directly translated into clinical practice. ML offers the potential to help refine risk stratification and increase accuracy to correctly predict clinical outcomes and disease classification. One of the complications in the clinical utilization of ML is that a large percentage of hematologists have limited familiarity with these tools which can cause skepticism. Concerns have also been raised by patients that are worried about privacy issues, reliability of the outcomes, and loss of human interaction. In this review, we aim to pinpoint the main mechanisms and applications of ML, as well as application in MN and Myelodysplastic Syndrome, highlighting strengths and limitations, and addressing the potential promise in clinical implementation of ML-pipelines.","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771772","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}

引用次数: 0

Immunocompetent mouse models of multiple myeloma. 免疫功能正常的多发性骨髓瘤小鼠模型。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-11-16 DOI: 10.1053/j.seminhematol.2024.11.003

Peter Leif Bergsagel, Marta Chesi

引用次数: 0

Melanoma antigen genes (MAGE); novel functional targets in multiple myeloma. 黑色素瘤抗原基因（MAGE）；多发性骨髓瘤的新功能靶点。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-28 DOI: 10.1053/j.seminhematol.2024.10.007

Anna Huo-Chang Mei, Alessandro Laganà, Roman Osman, Hearn Jay Cho

{"title":"Melanoma antigen genes (MAGE); novel functional targets in multiple myeloma.","authors":"Anna Huo-Chang Mei, Alessandro Laganà, Roman Osman, Hearn Jay Cho","doi":"10.1053/j.seminhematol.2024.10.007","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2024.10.007","url":null,"abstract":"Melanoma Antigen Genes (MAGE) are expressed in a broad range of cancers, including multiple myeloma. MAGE have been under investigation for more than 3 decades as targets for immune therapy, while in parallel, interrogation of their functions has revealed activities that may be particularly critical in multiple myeloma. MAGE-C1 is expressed in about 75% of newly diagnosed cases and this is maintained through the natural history of the disease. In contrast, MAGE-A3 is expressed in about 35% of newly diagnosed cases, but this increases to more than 75% after relapse. MAGE-A3 expression was associated with poor clinical outcome and resistance to chemotherapy. Translational studies have revealed that MAGE-A3 regulates cell cycling and apoptosis in myeloma cells. Genomic, gene expression, and multiomic studies demonstrate relations with high-risk subgroups of patients. MAGE-A3 mediates these functions through partnership with Kap1 to form a ubiquitin ligase complex. Structural analysis of the interaction between MAGE-A3 and Kap1 gives insight into the biochemical activity and substrate specificity and suggests novel pharmacologic strategies to inhibit them. These studies demonstrating MAGE-A3 oncogenic functions suggest that it may also be a suitable target for small molecule inhibition in multiple myeloma that may be broadly applicable to other cancers that express it.","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695903","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}

引用次数: 0

Modernizing multiple myeloma clinical trial eligibility to improve equity and inclusivity by hematological parameters. 多发性骨髓瘤临床试验资格现代化，通过血液学参数提高公平性和包容性。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-25 DOI: 10.1053/j.seminhematol.2024.10.008

Lauren Merz, Monique Hartley-Brown, Maureen Achebe, Craig Cole, Bindu Kanapuru, Ola Banjo, George Mulligan, Katie Wozniak, Anne Quinn Young, Hearn Jay Cho

{"title":"Modernizing multiple myeloma clinical trial eligibility to improve equity and inclusivity by hematological parameters.","authors":"Lauren Merz, Monique Hartley-Brown, Maureen Achebe, Craig Cole, Bindu Kanapuru, Ola Banjo, George Mulligan, Katie Wozniak, Anne Quinn Young, Hearn Jay Cho","doi":"10.1053/j.seminhematol.2024.10.008","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2024.10.008","url":null,"abstract":"In the United States, Black people experience multiple myeloma (MM) at a frequency that is more than double that of White people and experience much higher rates of mortality. Despite bearing a disproportionate impact of both MM incidence and mortality, Black patients are significantly underrepresented in most MM clinical trials. This is in part because Black patients experience a higher prevalence of hemoglobinopathies and Duffy-null phenotype, which affect hemoglobin and neutrophil levels, respectively, potentially excluding patients from clinical trials. The Multiple Myeloma Research Foundation (MMRF) has convened a series of Health Equity Summits that include a focus on creating inclusive clinical trials for MM. The present paper, an output of the most recent workshop, focuses on the role of laboratory reference ranges as a barrier to clinical trial participation and offers tangible steps to improve the enrollment of a diverse and representative population.","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710945","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}

引用次数: 0

Smoldering multiple myeloma: Integrating biology and risk into management. 燃烧性多发性骨髓瘤：将生物学和风险纳入管理。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-18 DOI: 10.1053/j.seminhematol.2024.10.002

Roshani Patel, Elizabeth Hill, Madhav Dhodapkar

引用次数: 0