文章：

FLT3突变白血病干细胞：耐药机制与新治疗靶点

FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets

原文发布日期：10 May 2024

DOI: 10.3390/cancers16101819

类型: Article

开放获取: 是

英文摘要：

Despite the availability of target drugs in the first and second line, only 30% of FLT3mut AMLs are cured. Among the multiple mechanisms of resistance, those of FLT3mut LSC are the most difficult to eradicate because of their metabolic and genomic characteristics. Reactivation of glycogen synthesis, inhibition of the RAS/MAPK pathway, and degradation of FLT3 may be potential aids to fight the resistance of LSC to FLT3i. LSC is also characterized by the expression of a CD34+/CD25+/CD123+/CD99+ immunophenotype. The receptor and ligand of FLT3, the natural killer group 2 member D ligand (NKGD2L), and CD123 are some of the targets of chimeric antigen receptor T cells (CAR-T), bispecific T-cell engager molecules (BiTEs), CAR-NK and nanoparticles recently designed and reported here. The combination of these new therapeutic options, hopefully in a minimal residual disease (MRD)-driven approach, could provide the future answer to the challenge of treating FLT3mut AML.

摘要翻译： 

尽管一线和二线治疗中已有靶向药物可用，但FLT3突变型急性髓系白血病（AML）的治愈率仅为30%。在众多耐药机制中，FLT3突变型白血病干细胞（LSC）因其代谢和基因组特征成为最难根除的耐药来源。重新激活糖原合成、抑制RAS/MAPK通路以及降解FLT3蛋白，可能成为克服LSC对FLT3抑制剂耐药性的潜在策略。LSC还具有CD34+/CD25+/CD123+/CD99+免疫表型特征。FLT3受体及其配体、自然杀伤细胞2族成员D配体（NKG2DL）以及CD123等靶点，已成为近期研发的嵌合抗原受体T细胞（CAR-T）、双特异性T细胞衔接器（BiTEs）、CAR-NK细胞及纳米颗粒等新型疗法的作用目标。若能以微小残留病（MRD）为导向，将这些新型治疗手段联合应用，有望为攻克FLT3突变型AML的治疗难题提供未来解决方案。

原文链接：

FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets