伴FUS/TLS∷ERG融合基因急性髓细胞白血病的研究现状  

Research status of acute myeloid leukemia with FUS/TLS∷ERG fusion gene

作　　者：王瑞芳 赵海涛[1] 郑永青[1] 孙明东[1] Wang Ruifang;Zhao Haitao;Zheng Yongqing;Sun Mingdong(Department of Hematology,Binzhou People′s Hospital,Binzhou 256600,Shandong Province,China)

机构地区：[1]滨州市人民医院血液科,滨州256600

出　　处：《国际输血及血液学杂志》2024年第3期224-232,共9页International Journal of Blood Transfusion and Hematology

基　　金：山东省医学会临床科研专项资金项目(YXH2022ZX03221)。

摘　　要：位于16p11.2的FUS/TLS基因与位于21q22.2的ERG基因融合形成FUS/TLS∷ERG,伴该融合基因急性髓细胞白血病(AML)是近年来报道的一类少见白血病,发生率<1%。FUS/TLS∷ERG融合蛋白由于FUS/TLS蛋白C末端结构域被ERG基因下游的DNA结合域取代而缺乏招募丝氨酸-精氨酸富集(SR)剪接因子的能力,导致RNA剪接的普遍减少。FUS/TLS∷ERG融合基因可显著增加髓系祖细胞的增殖和自我更新能力。该类AML患者临床特征包括发病年龄较轻,细胞形态学具有嗜酸性粒细胞增多、小巨核细胞增多、可见细胞吞噬和空泡现象等表现,免疫分型多表达CD56,可伴其他染色体异常和基因突变。伴FUS/TLS∷ERG融合基因AML患者疾病进展快、常规化疗难以获得完全缓解(CR),患者预后差,异基因造血干细胞移植(allo-HSCT)是该类患者的首选方法,但其克服融合基因所致不良预后的潜力仍需要进一步评估,并且如何减少移植后复发仍然是一项难题,需要继续探索新的治疗方法以改善患者的预后。The FUS/TLS gene located at 16p11.2 is fused with ERG gene located at 21q22.2 to form FUS/TLS∷ERG.acute myeloid leukemia(AML)accompanied by this fusion gene is a rare type of leukemia reported in recent years,with an incidence rate<1%.The FUS/TLS∷ERG fusion protein lacks the ability to recruit serine/arginine-rich(SR)splicing factors due to the replacement of the C-terminal domain of FUS/TLS protein by the DNA binding region downstream of ERG,leading to a general reduction in RNA splicing.The FUS/TLS∷ERG fusion gene significantly enhances the proliferation and self-renewal capacity of myeloid progenitor cells.The clinical features of this type of AML patients include a younger age of onset,Clinical features of this type of AML include younger age of onset,cytomorphologic manifestations of eosinophilia,small megakaryocytes,detectable phagocytosis and vacuolization,and a high expression of CD56 by immunophenotyping,which may be accompanied by other chromosomal abnormalities and gene mutations.AML patients with FUS/TLS∷ERG fusion gene were progresses rapidly,conventional chemotherapy is difficult to achieve complete remission(CR),and their prognosis were poor.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)appears to be the preferred treatment for such patients,but the potential to overcome its poor prognosis needs further evaluation.Moreover,how to decrease the recurrence of allo-HSCT remains a hard problem,and new therapeutic approaches are required to improve patients′prognosis.

关 键 词：TLS-ERG融合蛋白 人类 白血病 髓样 急性 基因 突变 造血干细胞移植 t(16 21)(p11 q22) 

分 类 号：R733.71[医药卫生—肿瘤]