成人<i>NUP98</i>重排相关急性髓系白血病的治疗进展

舒文婧; 沈杨

doi:10.13201/j.issn.1004-2806.2024.03.002

成人NUP98重排相关急性髓系白血病的治疗进展

舒文婧¹,
沈杨^1, ,

- 上海交通大学医学院附属瑞金医院血液科(上海，200025)

详细信息

作者简介:
沈杨，主任医师，博士生导师。担任国家转化医学中心血液清洁一病区主任。美国血液学会国际成员、中华医学会第九、十和十一届青年委员、中国医院协会血液学机构分会常委、中国卫生信息与健康医疗大数据学会慢病防治与管理专业委员会常委、中国抗癌协会肿瘤血液病学专业委员会委员、教育部学位评审专家、上海市抗癌协会委员。Frontiers in Oncology、Frontiers in Immunology客座主编。主要研究方向为急性白血病的分子分层及标志物和大数据研究。近年来以第一作者和通讯作者在Blood、Leukemia、PNAS、CCR、BCJ等杂志发表论文数十篇

通讯作者: 沈杨，E-mail：Shen_yang@126.com

中图分类号: R733.71

收稿日期: 2024-01-15

刊出日期: 2024-03-01

Progress in the treatment of adult acute myeloid leukaemia with NUP98 rearrangement

SHU Wenjing¹,
SHEN Yang^1, ,

- Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

More Information

Corresponding author: SHEN Yang, E-mail: Shen_yang@126.com

Received Date: 15 January 2024

Publish Date: 01 March 2024

摘要

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。
- 急性髓系白血病 /
- NUP98 /
- 基因重排
Abstract: 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.
- acute myeloid leukemia /
- NUP98 /
- gene rearrangement

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