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...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。展开更多
B-cell acute lymphoblastic leukemia(B-ALL)is a malignant tumor originating from B-lineage lymphoid precursor cells.The incidence of B-ALL is about 80%in childhood acute leukemia and 20%in adults.In recent years,with s...B-cell acute lymphoblastic leukemia(B-ALL)is a malignant tumor originating from B-lineage lymphoid precursor cells.The incidence of B-ALL is about 80%in childhood acute leukemia and 20%in adults.In recent years,with standardized treatment guided by risk stratification,the long-term disease-free survival rate of children is about 80%,while that of adults is less than 40%.However,the specific pathogenesis of the newly identified B-ALL and the targeted therapy strategies have not been vigorously investigated.In this review,we highlight the recent breakthroughs in mechanistic studies and novel therapeutic options in DUX4-and MEF2D-subtype B-ALLs.展开更多
文摘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。
基金This work was supported by research grants 81970132,81770142,81800144,and 31800642 from National Natural Science Foundation of Chinaa research grant 20JC1410600 from Shanghai Science and Technology Committee+1 种基金Shanghai Guangci Translational Medical Research Development Foundationa research grant 20152504 from“Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support”,“The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institute of Higher Learning”,Samuel Waxman Cancer Research Foundation。
文摘B-cell acute lymphoblastic leukemia(B-ALL)is a malignant tumor originating from B-lineage lymphoid precursor cells.The incidence of B-ALL is about 80%in childhood acute leukemia and 20%in adults.In recent years,with standardized treatment guided by risk stratification,the long-term disease-free survival rate of children is about 80%,while that of adults is less than 40%.However,the specific pathogenesis of the newly identified B-ALL and the targeted therapy strategies have not been vigorously investigated.In this review,we highlight the recent breakthroughs in mechanistic studies and novel therapeutic options in DUX4-and MEF2D-subtype B-ALLs.
