伴TP53基因异常骨髓增生异常肿瘤的临床研究进展

Clinical research progress on myelodysplastic neoplasms with TP53 gene abnormalities

骨髓增生异常肿瘤(myelodysplastic neoplasms,MDS)患者的预后与其细胞遗传学和分子遗传学特征密切相关,TP53基因作为MDS最常见的突变基因之一,其异常是MDS独立的不良预后因素以及向急性髓系白血病(acute myeloid leuke⁃mia,AML)转化的危险因素之一。新近更新的第5版世界卫生组织血液淋巴肿瘤分类标准(the 5th edition of the who classifica⁃tion of haematolymphoid tumours,WHO 2022)以及髓系肿瘤和急性白血病的国际共识分类(international consensus classification of myeloid neoplasms and acute leukemia,ICC)将伴有TP53双等位基因失活(biallelic TP53 inactivation,biTP53)的MDS作为独立的亚型列出,该亚型患者预后极差,生存期极短。目前针对伴TP53基因异常的MDS患者的治疗尚未能有效改善该类患者预后,新型靶向药物、免疫治疗等均在探索中,本文就国内外对伴TP53基因异常的MDS的临床研究进展进行综述。

The prognosis of patients with myelodysplastic neoplasms(MDS)is closely linked to their cytogenetic and molecular genetic characteristics.Among the most prevalent genetic mutations in MDS,the TP53 gene abnormalities stand out as an independent adverse prognostic factor for MDS and a significant risk factor for the progression to acute myeloid leukemia(AML).The recently updated 5th edition of the WHO classification of haematolymphoid tumours(WHO 2022)and international consensus classification of myeloid neoplasms and acute leukemia(ICC)recognizes MDS with TP53 biallelic inactivation(biTP53)as a distinct and independent subtype.Patients within this subtype face an exceedingly grim prognosis with an extremely short survival period.Currently,available treatments for MDS patients with TP53 gene abnormalities have proven ineffective in improving their prognosis.Consequently,there is a growing focus on exploring new avenues such as targeted therapies and immunotherapy.This article provides an in⁃depth review of the progress in clinical research related to MDS with TP53 gene abnormalities,both within domestic and international contexts.