上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2023 , Vol. 43 >Issue 5: 631 - 640

DOI: https://doi.org/10.3969/j.issn.1674-8115.2023.05.015

综述

ZNF384融合亚型急性白血病的发病机制及预后研究进展

  • 李瑛 ,
  • 谭阳霞 ,
  • 尹虹心 ,
  • 蒋雁翎 ,
  • 陈立 ,
  • 蒙国宇
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  • 1.昆明理工大学医学院基础医学系，昆明 650500
    2.上海交通大学医学院附属瑞金医院上海血液学研究所，医学基因组学国家重点实验室，国家转化医学研究中心（上海），上海 200025
李　瑛（1994—），女，硕士生；电子信箱：3258414023@qq.com。
蒙国宇，电子邮箱：guoyumeng@shsmu.edu.cn。

收稿日期: 2022-12-19

  录用日期: 2023-02-24

  网络出版日期: 2023-07-11

基金资助

国家自然科学基金(81970132)

收起

Research progress in the pathogenesis and prognosis of ZNF384 fusion subtype acute leukemia

  • Ying LI ,
  • Yangxia TAN ,
  • Hongxin YIN ,
  • Yanling JIANG ,
  • Li CHEN ,
  • Guoyu MENG
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  • 1.Department of Basic Medicine, School of Medicine, Kunming University of Science and Technology, Kunming 650500, China
    2.Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine(Shanghai), RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
MENG Guoyu, E-mail: guoyumeng@shsmu.edu.cn.

Received date: 2022-12-19

  Accepted date: 2023-02-24

  Online published: 2023-07-11

Supported by

National Natural Science Foundation of China(81970132)

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摘要

由染色体易位引起的融合基因已成为白血病的主要致病因素。锌指蛋白384（zinc finger protein 384，ZNF384）融合作为急性白血病（acute leukemia，AL）中的非典型融合亚型，在不同的年龄群体中广泛发生。ZNF384具有丰富的融合伴侣，其中E1A结合蛋白p300（E1A binding protein p300，EP300）、转录因子3（transcription factor 3，TCF3）、TATA-box binding protein associated factor 15（TAF15）的融合频率最高。这些融合蛋白均保留了完整的ZNF384结构，但融合伴侣则有不同程度的缺失，说明不同的ZNF384融合亚型之间具有相似的致AL发生发展机制。现有研究主要认为ZNF384融合蛋白通过染色质重塑调控下游蛋白的转录表达，在造血干细胞的分化、癌细胞的增殖凋亡和基因组修复中发挥潜在作用。ZNF384融合患者同时表达淋系和髓系特有的抗原，在疾病的进展中具有谱系转化特性，丰富的免疫表型给治疗方式带来了不确定性，并与融合亚型、发病年龄一起影响患者的临床结局。该文通过对近10年已发表的案例和大型队列研究进行统计归纳分析，进一步确认了ZNF384融合及其各亚型AL在现有研究背景下的发生频率，总结了已有的机制信息，并对不同治疗方式下ZNF384融合患者的预后作了简要分析，以期为后续针对这一独特亚型AL的诊疗和研究提供参考。

关键词： ZNF384融合; 急性白血病; 免疫表型; 机制; 诊断; 预后

本文引用格式

李瑛 , 谭阳霞 , 尹虹心 , 蒋雁翎 , 陈立 , 蒙国宇 . ZNF384融合亚型急性白血病的发病机制及预后研究进展[J]. 上海交通大学学报（医学版）, 2023 , 43(5) : 631 -640 . DOI: 10.3969/j.issn.1674-8115.2023.05.015

Abstract

Gene fusions caused by chromosomal translocations have become the main pathogenic factors that initiate leukemogenesis. Zinc finger protein 384 (ZNF384) fusion, as an atypical fusion gene in acute leukemia (AL), has widely been identified in different age groups. ZNF384 rearranged 18 genes, with E1A binding protein p300 (EP300), transcription factor 3, (TCF3), and TATA-box binding protein-associated factor 15 (TAF15) being the most common fusion partners. These fusion proteins maintain the complete structure of ZNF384, but the fusion partners are missing in varying degrees, indicating that the mechanisms behind different subtypes of carcinogenesis have similarities. The mechanism of ZNF384-rearranged AL is also being actively investigated. It is mainly believed that the fusion protein regulates the transcription and expression of downstream proteins through chromatin remodeling, and plays a potential role in the differentiation of hematopoietic stem cells, the proliferation and apoptosis of cancer cells and genome repair. Patients with ZNF384 fusions express both lymphoid and myeloid-specific antigens, which have lineage-transforming properties during disease progression. The diversity of immunophenotypes leads to ambiguity in treatment options and diverse outcomes in prognosis studies, and affects the clinical outcome of patients together with fusion subtype and age of onset. Through the statistical analysis of published cases and large-scale cohort studies in the past 10 years, the incidence of ZNF384 fusion in AL and the frequency of each fusion subtype in the context of existing research were further confirmed. The impact of different treatment methods on the prognosis of patients was analyzed, and the identified mechanisms were summarized in order to provide reference for subsequent diagnosis, treatment and research of this unique AL subtype.

Key words： ZNF384 fusion; acute leukemia (AL); immunophenotype; mechanism; diagnosis; prognosis

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