p53在5q-综合征发病机制中的研究现状  

Research status of p53 in the pathogenesis of 5q-syndrome

作　　者：羊文莉 佟红艳[1] Yang Wenli;Tong Hongyan(Department of Hematology,First Affiliated Hospital,Zhejiang University School of Medicine,Myelodysplastic Syndromes Diagnosis and Therapy Center,Hangzhou 310003,Zhejiang Province,China)

机构地区：[1]浙江大学医学院附属第一医院血液科,MDS中心,杭州310003

出　　处：《国际输血及血液学杂志》2021年第1期7-13,共7页International Journal of Blood Transfusion and Hematology

基　　金：国家自然科学基金(89107117、81700121、81800121)。

摘　　要：5q-综合征是骨髓增生异常综合征(MDS)的特殊亚型,该病患者的临床表现以贫血为主,血小板计数可正常或增高,骨髓原始细胞比例<5%,预后较好。随着对5q-综合征研究的进展,其发病机制逐渐被揭示。位于5号染色体长臂(5q)的CSNK1A1、RPS14、EGR1等致病基因单倍剂量不足,是引起该病不同临床表型的主要分子机制,其中多个基因的缺失与TP53的表达产物p53相关。此外,伴5号染色体异常MDS患者的TP53突变率较MDS总体人群明显升高,因此p53在5q-综合征的发病机制中发挥重要作用,并已成为其潜在治疗靶点。目前,来那度胺为5q-综合征的一线用药,其作用机制也与p53相关。笔者拟就RPS14、CSNK1A1、EGR1等关键致病基因单倍剂量不足、TP53突变通过p53参与5q-综合征的发病,以及来那度胺通过p53对5q-综合征发挥治疗作用等方面,对p53在5q-综合征发病机制中的研究现状进行阐述。5q-syndrome is a distinct subtype of myelodysplastic syndrome(MDS).Its clinical manifestations were anemia,normal or increased platelet count and bone marrow blasts<5%.Patients with 5q-syndrome have a comparatively better prognosis than other subtypes of MDS.As research progresses,the pathogenesis of 5q-syndrome is gradually revealed.The haploinsufficiency of CSNK1A1,RPS14,EGR1 and other genes in the long arm of chromosome 5(5q)are the molecular mechanisms of its phenotype,and the absence of these genes are related to p53,which is the expression product of TP53.Besides,the mutation rate of TP53 in MDS patients with chromosome 5 abnormalities is higher than the total MDS patients.Thus p53 plays an important role in pathogenesis of 5q-syndrome,which has become a potential therapeutic target.And the mechanisms of lenalidomide,as the first-line drug for 5q-syndrome,is also related to p53.This article provides an overview of the pathogenesis of p53 in the 5q-syndrome,including molecular mechanisms of the haploinsufficiency of RPS14、CSNK1A1、EGR1 and TP53 mutation,as well as the effects of lenalidomide targeting on p53.

关 键 词：骨髓增生异常综合征 染色体缺失 基因 p53 5Q-综合征 RPS14 CK1α 

分 类 号：R551.3[医药卫生—血液循环系统疾病]