·综述·doi:10.3969/j.issn.1671-8348.2023.08.024网络首发网络首发:https://kns.cnki.net/kcms/detail//50.1097.R.20230130.1557.013.html(2023-01-30)ASXL1突变促进高危MDS患者疾病进展的机制及潜在治疗靶点*黄龄乐综述,王利△审校(重庆医科大学附属第一医院血液内科400016)[摘要]骨髓增生异常综合征(MDS)是一种异质性的髓系克隆性造血疾病,以骨髓造血功能异常、外周血细胞减少及急性髓系白血病转化风险增加为特点。附加性梳样结构1(ASXL1)突变是MDS患者常见基因突变,尤其在国际预后积分系统(IPSS)危险分层的高危组或进展期患者中发生频率更高,且提示预后不良。ASXL1突变蛋白通过干扰与组蛋白相互作用,影响染色质凝缩状态调控基因表达。该文对ASXL1突变在高危MDS患者中的生理病理机制做一综述,并总结了潜在治疗靶点。[关键词]骨髓增生异常综合征;附加性梳样结构1;突变;治疗;综述[中图法分类号]R551.3[文献标识码]A[文章编号]1671-8348(2023)08-1242-06MechanismofASXL1mutationinpromotingdiseaseprogressioninhigh-riskMDSpatientsandpotentialtherapeutictarget*HUANGLingle,WANGLi△(DepartmentofHematology,theFirstAffiliatedHospitalofChongqingMedicalUniversity,Chongqing400016,China)[Abstract]Myelodysplasticsyndrome(MDS)isaheterogeneousmyeloidclonalhematopoieticdiseasecharacterizedbyabnormalhematopoieticfunctionofbonemarrow,peripheralbloodcellsdecreaseandacutemyeloidleukemiatransformingriskincrease.Theadditionalsexcombs-like1(ASXL1)mutationisacommongenemutationinMDSpatients,itsoccurrencefrequencyishigherespeciallyinthehigh-riskgrouporprogres-sivestagepatientsoftheInternationalPrognosticScoringSystem(IPSS),moreoverwhichindicatingapoorprognosis.TheASXL1mutantproteinaffectsthecondensationofchromatintoregulatedgeneexpressionbyinterferingwiththeinteractionwithhistones.Thisarticlereviewsthephysiologicalandpathologicalmecha-nismsofASXL1mutationinhigh-riskMDSpatients,andsummarizesthepotentialtherapeutictargets.[Keywords]myelodysplasticsyndrome;additionalsexcombs-like1;mutation;treatment;reveiw骨髓增生异常综合征(myelodysplasticsyn-drome,MDS)是髓系造血异常相关血液系统疾病,80%以上的MDS患者常常伴有遗传学异常,包括染色体异常和基因突变,其中发生频率较高的基...
