{"title":"骨髓增生异常综合征贫血的致病机制和靶向治疗","authors":"Doudou Chang , Linhua Yang , Ruijuan Zhang","doi":"10.1016/j.leukres.2025.108099","DOIUrl":null,"url":null,"abstract":"<div><div>Myelodysplastic Syndromes (MDS) are malignant neoplasms of the myeloid lineage originating from hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis, blood cell dysplasia, and a high risk of transformation to acute leukemia. Anemia affects up to 90 % of MDS patients, significantly increasing symptom burden, impacting quality of life, accelerating disease progression, and is associated with increased morbidity and mortality. The limited therapeutic landscape for addressing anemia in MDS presents a significant challenge in clinical management. This review explores the mechanisms of anemia in MDS(including low-risk MDS and high-risk MDS), covering disturbances in hematopoiesis, telomere dynamics, inflammation, immune dysregulation, alterations in iron metabolism, and the role of the bone marrow microenvironment. We examine how these factors contribute to the complex pathophysiology of MDS-related anemia and discuss their implications for treatment strategies. Furthermore, we highlight recent advances in understanding the molecular basis of MDS, which have paved the way for novel therapeutic approaches. These include targeted therapies addressing specific genetic mutations, immunomodulatory agents, and innovative approaches to stimulate effective erythropoiesis. We also review emerging treatments such as Luspatercept, along with other novel agents targeting specific pathways, and ongoing clinical trials exploring combination therapies and personalized treatment strategies.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"158 ","pages":"Article 108099"},"PeriodicalIF":2.2000,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pathogenic mechanisms and targeted therapies for anemia in myelodysplastic syndromes\",\"authors\":\"Doudou Chang , Linhua Yang , Ruijuan Zhang\",\"doi\":\"10.1016/j.leukres.2025.108099\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Myelodysplastic Syndromes (MDS) are malignant neoplasms of the myeloid lineage originating from hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis, blood cell dysplasia, and a high risk of transformation to acute leukemia. Anemia affects up to 90 % of MDS patients, significantly increasing symptom burden, impacting quality of life, accelerating disease progression, and is associated with increased morbidity and mortality. The limited therapeutic landscape for addressing anemia in MDS presents a significant challenge in clinical management. This review explores the mechanisms of anemia in MDS(including low-risk MDS and high-risk MDS), covering disturbances in hematopoiesis, telomere dynamics, inflammation, immune dysregulation, alterations in iron metabolism, and the role of the bone marrow microenvironment. We examine how these factors contribute to the complex pathophysiology of MDS-related anemia and discuss their implications for treatment strategies. Furthermore, we highlight recent advances in understanding the molecular basis of MDS, which have paved the way for novel therapeutic approaches. These include targeted therapies addressing specific genetic mutations, immunomodulatory agents, and innovative approaches to stimulate effective erythropoiesis. We also review emerging treatments such as Luspatercept, along with other novel agents targeting specific pathways, and ongoing clinical trials exploring combination therapies and personalized treatment strategies.</div></div>\",\"PeriodicalId\":18051,\"journal\":{\"name\":\"Leukemia research\",\"volume\":\"158 \",\"pages\":\"Article 108099\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0145212625005892\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0145212625005892","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Pathogenic mechanisms and targeted therapies for anemia in myelodysplastic syndromes
Myelodysplastic Syndromes (MDS) are malignant neoplasms of the myeloid lineage originating from hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis, blood cell dysplasia, and a high risk of transformation to acute leukemia. Anemia affects up to 90 % of MDS patients, significantly increasing symptom burden, impacting quality of life, accelerating disease progression, and is associated with increased morbidity and mortality. The limited therapeutic landscape for addressing anemia in MDS presents a significant challenge in clinical management. This review explores the mechanisms of anemia in MDS(including low-risk MDS and high-risk MDS), covering disturbances in hematopoiesis, telomere dynamics, inflammation, immune dysregulation, alterations in iron metabolism, and the role of the bone marrow microenvironment. We examine how these factors contribute to the complex pathophysiology of MDS-related anemia and discuss their implications for treatment strategies. Furthermore, we highlight recent advances in understanding the molecular basis of MDS, which have paved the way for novel therapeutic approaches. These include targeted therapies addressing specific genetic mutations, immunomodulatory agents, and innovative approaches to stimulate effective erythropoiesis. We also review emerging treatments such as Luspatercept, along with other novel agents targeting specific pathways, and ongoing clinical trials exploring combination therapies and personalized treatment strategies.
期刊介绍:
Leukemia Research an international journal which brings comprehensive and current information to all health care professionals involved in basic and applied clinical research in hematological malignancies. The editors encourage the submission of articles relevant to hematological malignancies. The Journal scope includes reporting studies of cellular and molecular biology, genetics, immunology, epidemiology, clinical evaluation, and therapy of these diseases.