Seminars in hematology最新文献_第3页

Cellular and immunotherapies for myelodysplastic syndromes 骨髓增生异常综合征的细胞和免疫疗法。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-12-01 DOI: 10.1053/j.seminhematol.2024.09.006

Ryan J. Stubbins , Hannah Cherniawsky , Aly Karsan

{"title":"Cellular and immunotherapies for myelodysplastic syndromes","authors":"Ryan J. Stubbins , Hannah Cherniawsky , Aly Karsan","doi":"10.1053/j.seminhematol.2024.09.006","DOIUrl":"10.1053/j.seminhematol.2024.09.006","url":null,"abstract":"<div><div>In this review article, we outline the current landscape of immune and cell therapy-based approaches for patients with myelodysplastic syndromes (MDS). Given the well characterized graft-versus-leukemia (GVL) effect observed with allogeneic hematopoietic cell transplantation, and the known immune escape mechanisms observed in MDS cells, significant interest exists in developing immune-based approaches to treat MDS. These attempts have included antibody-based drugs that block immune escape molecules, such as inhibitors of the PD-1/PD-L1 and TIM-3/galectin-9 axes that mediate interactions between MDS cells and T-lymphocytes, as well as antibodies that block the CD47/SIRPα interaction, which mediates macrophage phagocytosis. Unfortunately, these approaches have been largely unsuccessful. There is significant potential for T-cell engaging therapies and chimeric antigen receptor T (CAR-T) cells, but there are also several limitations to these approaches that are unique to MDS. However, many of these limitations may be overcome by the next generation of cellular therapies, including those with engineered T-cell receptors or natural killer (NK)-cell based platforms. Regardless of the approach, all these immune cells are subject to the complex bone marrow microenvironment in MDS, which harbours a variable and heterogeneous mix of pro-inflammatory cytokines and immunosuppressive elements. Understanding this interaction will be paramount to ensuring the success of immune and cellular therapies in MDS.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 6","pages":"Pages 397-408"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473899","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

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 DOI: 10.1053/j.seminhematol.2024.09.007

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

{"title":"Understanding MDS stem cells: Advances and limitations","authors":"Sweta B. Patel , Daniel R. Moskop , Craig T. Jordan, Eric M. Pietras","doi":"10.1053/j.seminhematol.2024.09.007","DOIUrl":"10.1053/j.seminhematol.2024.09.007","url":null,"abstract":"<div><div>In work spanning several decades, extensive studies have focused on the properties of malignant stem cells that drive the pathogenesis of acute myeloid leukemia (AML). However, relatively little attention has been devoted to several serious myeloid malignancies that occur prior to the onset of frank leukemia, including myelodysplastic syndrome (MDS). Like leukemia, MDS is hypothesized to arise from a pool of immature malignant stem and progenitor cells (MDS-SCs) that serve as a reservoir for disease evolution and progression<sup>1</sup>. While multiple studies have sought to identify and characterize the biology and vulnerabilities of MDS-SCs, yet translation of scientific concepts to therapeutically impactful regimens has been limited. Here, we evaluate the currently known properties of MDS-SCs as well as the post-transcriptional mechanisms that drive MDS pathogenesis at a stem and progenitor level. We highlight limits and gaps in our characterization and understanding of MDS-SCs and address the extent to which the properties of MDS-SC are (and can be) inferred from the characterization of LSCs.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 6","pages":"Pages 409-419"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547224","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

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 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":"<div><div>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.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 6","pages":"Pages 470-478"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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 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":"<div><div>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.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 6","pages":"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 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 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. 机器学习在骨髓增生异常综合征中的潜在前景。

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":"<p><p>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.</p>","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

CARs Moving Forward: The Development of CAR T-Cell Therapy in the Earlier Treatment Course of Hematologic Malignancies CARs 勇往直前：CAR T 细胞疗法在血液恶性肿瘤早期治疗过程中的发展。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.08.005

Omar Castaneda Puglianini , Julio C. Chavez

引用次数: 0

CAR T-cell therapy comes of age: Introductory editorial for the special issue CAR T 细胞疗法时代的到来：特刊序言

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.10.003

Jennifer N. Brudno MD

引用次数: 0

The Road More or Less Traveled- Examining the Role of Consolidative Allogeneic Hematopoietic Stem Cell Transplantation After Chimeric Antigen Receptor T Cell Therapy in B-cell ALL 多行不义必自毙--研究嵌合抗原受体T细胞疗法在B细胞ALL中的异基因造血干细胞移植的作用。