Department of Biomedicine and Prevention, University of Tor Vergata.
Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
Curr Opin Oncol. 2024 Nov 1;36(6):569-576. doi: 10.1097/CCO.0000000000001094. Epub 2024 Aug 26.
FLT3 mutations are among the most common myeloid drivers identified in adult acute myeloid leukemia (AML). Their identification is crucial for the precise risk assessment because of the strong prognostic significance of the most recurrent type of FLT3 alterations, namely internal tandem duplications (ITDs). Recent advances in the pathogenesis and biology of FLT3 -mutated AML have opened an opportunity for development and application of selective inhibition of FLT3 pathway.
In the last decade, at least three targeted treatments have been approved by regulatory agencies and several others are currently under investigations. Here, we review the latest advance in the role of FLT3 mutations in AML, providing an outline of the available therapeutic strategies, their mechanisms of actions and of resistance, as well as routes for potential improvement.
The availability of FLT3 inhibitors has improved outcomes in AML harboring such mutations, currently also reflected in disease stratification and recommendations. Newer inhibitors are under investigations, and combinations with chemotherapy or other targeted treatments are being explored to further improve disease outcomes.
FLT3 突变是成人急性髓系白血病（AML）中最常见的髓系驱动因素之一。由于最常见的 FLT3 改变类型——内部串联重复（ITD）具有很强的预后意义，因此鉴定其对于精确的风险评估至关重要。FLT3 突变 AML 的发病机制和生物学的最新进展为 FLT3 通路的选择性抑制的开发和应用提供了机会。
在过去的十年中，至少有三种靶向治疗方法已被监管机构批准，还有其他几种方法正在研究中。在这里，我们综述了 FLT3 突变在 AML 中的最新作用进展，概述了现有的治疗策略、它们的作用机制和耐药机制，以及潜在的改进途径。
FLT3 抑制剂的出现改善了携带此类突变的 AML 的预后，目前这也反映在疾病分层和推荐中。新型抑制剂正在研究中，正在探索与化疗或其他靶向治疗联合应用，以进一步改善疾病结局。
