FLT3突变多样性及对急性髓系白血病预后的影响  

Heterogeneity of FLT3 mutations and prognostic implications in acute myeloid leukemia

作　　者：郭建刚 吴庭恺 于晓达 王安安 李佳璟 刘蓓[3] Jiangang Guo;Tingkai Wu;Xiaoda Yu;Anan Wang;Jiajing Li;Bei Liu(The First Clinical Medical College of Lanzhou University,Lanzhou 730000,China;Department of Hematology,Gansu Province Central Hospital,Lanzhou 730000,China;Department of Hematology,The First Hospital of Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学第一临床医学院,兰州市730000 [2]甘肃省中心医院血液科 [3]兰州大学第一医院血液科

出　　处：《中国肿瘤临床》2024年第23期1212-1217,共6页Chinese Journal of Clinical Oncology

基　　金：甘肃省自然科学基金项目(编号:24JRRA297)资助。

摘　　要：目的:探讨FLT3突变多样性及共突变对急性髓系白血病(acute myeloid leukemia,AML)患者临床特征和预后的影响。方法:回顾性分析2017年10月至2024年3月就诊于兰州大学第一医院经基因检测携带FLT3突变的80例AML患者临床特征,评估FLT3突变频率、碱基插入长度、位点、共突变对生存的影响。结果:FLT3-ITD突变的变异等位基因频率(variant allele frequency,VAF)与初诊AML患者白细胞计数、乳酸脱氢酶水平相关,插入位点与碱基插入长度相关。VAF≥0.38的AML患者总生存期(overall survival,OS)缩短,FLT3-ITD碱基插入长度、插入位点、突变个数与OS无关。非经典FLT3突变与FLT3-ITD突变患者相比OS显著延长。同时携带(FLT3-ITD、NPM1、DNMT3A)三突变患者OS明显缩短。使用FLT3抑制剂及异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)可改善FLT3-ITD突变患者的预后。结论:FLT3多样性与AML患者的临床特征及预后相关。非典型FLT3突变及FLT3-TKD突变预后较好。VAF≥0.38患者预后较差,但使用FLT3抑制剂可改善其预后。三突变患者预后较差。Objective:To investigate the heterogeneity of FLT3 mutations and the consequences of co-occurring mutations on the clinical features and prognosis of patients with acute myeloid leukemia(AML).Methods:We retrospectively analyzed the clinical characteristics of 80 patients with AML who carried FLT3 mutations,as detected by genetic testing,and were treated in The First Hospital of Lanzhou University from October 2017 to March 2024.An analysis was performed to evaluate the impact of FLT3 mutation frequency,insertion length of base pairs,insertion site,and co-occurring mutations on survival outcomes.Results:The variant allele frequency(VAF)of FLT3-ITD mutations was correlated with leukocyte counts and lactate dehydrogenase levels in patients with de novo AML.There was an association between the insertion site and the length of the base-pair insertion.Patients with AML who also had a VAF of FLT3-ITD mutations greater than or equal to 0.38 exhibit reduced overall survival(OS),whereas the length of base pair insertion,insertion site,and number of mutations did not correlate with OS.Patients with non-classical FLT3 mutations demonstrated a significantly longer OS than did those with FLT3-ITD mutations.The co-occurrence of FLT3-ITD,NPM1,and DNMT3A mutations was associated with markedly reduced OS.The use of FLT3 inhibitors and allogeneic hematopoietic stem cell transplantation(allo-HSCT)can improve the prognosis of patients with FLT3-ITD mutations.Conclusions:FLT3 mutational heterogeneity correlates with the clinical characteristics and outcomes of patients with AML.Non-classical FLT3 and FLT3-TKD mutations are associated with superior prognosis.Patients with a VAF of 0.38 or higher have a poorer prognosis,but the use of FLT3 inhibitors can improve their prognosis.Patients with triple mutations have poor prognosis.

关 键 词：FLT3 急性髓系白血病 共突变 预后 

分 类 号：R73[医药卫生—肿瘤]