Inhibition of FLT3:A Prototype for Molecular Targeted Therapy in Acute Myeloid Leukemia

作     者：Meira Yisraeli Salman Jacob M.Rowe Nir Weigert Meira Yisraeli Salman;Jacob M.Rowe;Nir Weigert

作者机构：Department of HematologyShaare Zedek Medical CenterJerusalem 9103102Israel Department of Hematology and Bone Marrow TransplantationRambam Medical CenterHaifa 3109601Israel Technion—Israel Institute of TechnologyHaifa 3200003Israel 

出 版 物：《Engineering》 (工程（英文）)

年 卷 期：2021年第7卷第10期

页      面：1354-1368页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：We wish to thank Beth Zisman for assistance in the preparation of this manuscript. Meira Yisraeli Salman  Jacob M. Rowe  and Nir Weigert declare that they have no conflict of interest or financial conflicts to disclose 

主　　题：AML Targeted therapy FLT3 inhibitors Midostaurin Gilteritinib Quizartinib Sorafenib 

摘      要：Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of *** AML diagnosis was dependent on morphology,aided initially only by *** acute lymphoblastic leukemia(ALL),immunophenotyping offered little in the diagnosis of AML,at least during the 1970s and *** advent of reliable cytogenetics changed the entire prognostic outlook of *** karyotypic analysis,different groups of AML could be classified and stratified for various *** mutational profiling was a major advance in further categorizing AML patients,aided by the immunophenotypic identification of antigenic markers on the *** these advances were occurring as the understanding of the importance of the tumor burden—known as minimal residual disease(MRD)—became crucial for the management of AML *** efficacy of MRD has rapidly progressed in the past decade,from a specificity of 10
3 with immunophenotyping to 10
4 with polymerase chain reaction(PCR),which is only appropriate for some patients with AML,and finally to 10
5 or even 10
6 cells with the extraordinary sensitivity of next-generation sequencing(NGS).All of these advances have promoted the concept of personalized medicine,which has led to the advent of targeted agents that can accurately be used for specific diagnostic *** can be predicted and measured *** targeted agents have now become a cornerstone in the management of AML,increasing effi-cacy and dramatically reducing *** focus of this review is on one of the most well-studied targeted agents in AML:the FMS-like tyrosine kinase 3(FLT3)inhibitors,which have impacted the prognostication and therapeutics of *** review selectively discusses the FLT3 inhibitors in detail,as a model for the other burgeoning targeted agents that have already been approved,as well as tho