肿瘤细胞治疗研究
英文原题：FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets.
FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets.
尽管一线和二线已有靶向药物可用，但只有 30% 的 FLT3mut AML 被治愈。
尽管已有一线和二线靶向药物，FLT3 突变型急性髓系白血病（AML）仍仅有 30% 可治愈。在多种耐药机制中，FLT3 突变型白血病干细胞（LSC）因其代谢和基因组特征而最难清除。重新激活糖原合成、抑制 RAS/MAPK 通路及降解 FLT3，可能有助于克服 LSC 对 FLT3 抑制剂（FLT3i）的耐药。LSC 还具有 CD34+/CD25+/CD123+/CD99+ 免疫表型。FLT3 受体及其配体、NK 细胞 2D 组配体（NKG2DL）和 CD123，是近期设计并在本文报道的CAR-T 细胞、双特异性 T 细胞衔接分子（BiTE）、CAR-NK 和纳米颗粒疗法的若干靶点。将这些新型治疗方式联合起来，并有望采用由微小残留病灶（MRD）指导的治疗方案，可能为未来应对 FLT3 突变型 AML 治疗挑战提供答案。
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.
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