罗特西普在SF3B1突变骨髓增生异常综合征治疗中的研究进展

Research progress of luspatercept in the treatment of SF3B1-mutated myelodysplastic syndrome

骨髓增生异常综合征(myelodysplastic syndrome,MDS)是一种起源于造血干细胞(hematopoietic stem cells,HSCs)的异质性髓系肿瘤,并有进展为急性髓性白血病(acute myeloid leukemia,AML)的高风险。约90%的MDS患者存在基因突变,其中25%存在SF3B1突变,发生此突变的MDS患者TGF-β通路表达上调,诱导细胞周期阻滞,从而表现为红系无效造血、病态造血。罗特西普可作为配体陷阱捕获TGF-β配体,抑制SMAD2/3通路激活,下调TGF-β通路,促进晚期红细胞成熟。目前,罗特西普已被美国食品药品监督管理局(FDA)批准用于改善低危MDS患者贫血的治疗,并且其在SF3B1突变患者中反应率更高。本文将对罗特西普治疗SF3B1突变相关MDS的现状予以综述,分析其有效性与安全性,以期为临床使用提供治疗策略。

Myelodysplastic syndrome(MDS)is a heterogeneous myeloid tumor that originates from hematopoietic stem cells(HSCs)and is associated with a high risk of progression to acute myeloid leukemia(AML).Studies have shown that 90%of patients with MDS have gene mutations,of whom approximately 25%have SF3B1 mutations.In patients with MDS carrying this mutation,the TGF-βpathway is upregulated,inducing cell cycle arrest and thereby leading to erythroid ineffective hematopoiesis and pathological hematopoiesis.Luspatercept can be used as a ligand trap to capture TGF-βligands,inhibit SMAD2/3 pathway activation,downregulate TGF-βpathway,and promote advanced red blood cell maturation.Currently,it has been approved by the Food and Drug Administration(FDA)for the treatment of anemia in patients with low-risk MDS,and studies have shown that the response rate is higher in patients with SF3B1 mutations.This article will review the current status of luspatercept in the treatment of SF3B1 mutation-related MDS;it will also analyze its effectiveness and safety and provide therapeutic strategies for clinical use.