Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine  

作　　者：Sai Huang Peng Chen Lu Wang Lingmin Xu Nan Wang Fei Li Liping Dou Daihong Liu 

机构地区：[1]Department of Hematology,Senior Department of Hematology,The Fifth Medical Center of PLA General Hospital,Bejing 100039,China [2]National Clinical Research Center of Geriatric Diseases,Chinese PLA General Hospital,Bejing 100853,China Chinese [3]PLA Medical School,Beijing 100853,China [4]Department of Hematology,The First Medical Center of PLA General Hospital,Bejing 100853,China

出　　处：《Cancer Pathogenesis and Therapy》2024年第2期112-120,共9页癌症发生与治疗（英文）

基　　金：supported by the National Natural Science Foundation of China(Nos.82200169,82270162,82270224,and 82070178);the National Key R&D Program of China(No.2021YFA1100904);the Beijing Natural Science Foundation of China(No.7222175);the Military Medical Support Innovation and Generate Special Program(No.21WQ034);the Special Research Fund for Health Protection(No.21BJZ30).

摘　　要：Background:Acute myeloid leukemia(AML)is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers.Decitabine,a deoxyribonucleic acid(DNA)methyltransferase(DNMT)in-hibitor,combined with cytarabine,aclarubicin hydrochloride,and granulocyte colony-stimulating factor(DCAG),has been used in patients newly diagnosed with AML.This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities,as well as those with specific gene mutations.However,the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined.Therefore,this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML.Methods:This study analyzed the clinical data and genetic mutations based on next-generation sequencing(NGS)in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army(PLA)General Hospital from January 2008 to August 2020.Factors associated with the cumulative incidence of relapse(CIR)and leukemia-free survival(LFS)in patients newly diagnosed with AML were analyzed.Results:The most adverse prognosis of DCAG-treated patients was observed in those with FLT3-ITD,KIT,PTPN11,GATA2,or IDH1 mutations during univariable analysis,whereas PTPN11 mutation was solely significant in multivariable analysis,with an increased likelihood of CIR(P=0.001)and reduced LFS duration(P=0.077).Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk(P=0.044)and decreased LFS duration(P=0.042)in multivariable analysis.In this study,we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range.Conclusion:NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations,indicating the need for new therapies that target this high-risk subtype of AML.These results offer a po

关 键 词：Acute myeloid leukemia Next-generation sequencing Prognosis DNA methyltransferase CHEMOTHERAPY 

分 类 号：R733.71[医药卫生—肿瘤]