摘要
急性髓系白血病(acute myeloid leukaemia,AML)伴NUP98重排作为AML的罕见亚型,在《第5版造血与淋巴组织肿瘤分类》伴重现性遗传学异常AML分类中被单独归为一类。这种亚型通常在儿童AML中相对较为多见,但在成人中检出率仅为2%左右。NUP98基因可与其多种融合伴侣共同参与AML的发病过程,其中包括HOX基因家族和其他非HOX基因,同时常伴有其他突变如FLT3-ITD、WT1、NRAS等。在成人AML中,NUP98基因重排主要以NUP98∷HOXA9和NUP98∷NSD1为主。各种实验证明NUP98重排具有白血病致病性,其融合蛋白通过影响转录调控、染色质重塑等机制,促使白血病的发生。同时,NUP98重排的患者在临床上表现出独特的特征,如好发于年轻、女性患者,伴有明显的出血症状。这类患者的预后通常较差,复发率高。目前治疗NUP98重排AML仍面临挑战,缺乏特异的靶向药物,但异基因造血干细胞移植在改善预后方面显示出显著疗效。因此,NUP98基因重排AML作为成人AML中的罕见高危亚型,需要进一步深入研究开发更为有效的治疗策略。
Acute myeloid leukaemia(AML)with NUP98 rearrangement is classified as a new separate category of AML with defining genetic abnormalities in the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours.This rare subtype is usually relatively common in children with AML but only occurs in about 2%of adults.NUP98 gene can participate in the pathogenesis of AML with a variety of fusion partners,including HOX genes and non-HOX genes,and is often accompanied by other mutations such as FLT3-ITD,WT1,and NRAS.In adult AML,NUP98 gene rearrangements are mainly dominated by NUP98∷HOXA9 and NUP98∷NSD1.Various experiments have demonstrated that the NUP98 fusion oncoproteins can drive leukemogenesis by affecting transcriptional regulation,chromatin remodeling,and other mechanisms.Patients with NUP98 rearrangement exhibit distinctive clinical features,including evident bleeding symptoms and a worse outcome,with a higher prevalence among young females.Currently,the treatment of NUP98 rearrangement AML is confronted with challenges,lacking specific targeted drugs.Nevertheless,allogeneic hematopoietic stem cell transplantation has shown significant efficacy in improving prognosis.Therefore,NUP98-rearranged AML defined as a rare and high-risk leukemia subset,requires further more extensive research to develop better therapeutic strategies.
作者
舒文婧
沈杨
SHU Wenjing;SHEN Yang(Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China)
出处
《临床血液学杂志》
CAS
2024年第3期150-155,共6页
Journal of Clinical Hematology
