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 patients. Accurate AML diagnosis was dependent on morphology, aided initially only by cytochemistry. Unlike acute lymphoblastic leukemia (ALL), immunophenotyping offered little in the diagnosis of AML, at least during the 1970s and 1980s. The advent of reliable cytogenetics changed the entire prognostic outlook of AML. With karyotypic analysis, different groups of AML could be classified and stratified for various therapies. Unique mutational profiling was a major advance in further categorizing AML patients, aided by the immunophenotypic identification of antigenic markers on the cells. All 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 patients. The 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 subtypes. Responses can be predicted and measured accurately. Such targeted agents have now become a cornerstone in the management of AML, increasing efficacy and dramatically reducing toxicity. The 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 AML. This 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 those that are currently in development.

急性髓系白血病 (AML) 的现代治疗始于 1973 年，首次报道柔红霉素和阿糖胞苷的成功联合治疗使大约 45% 的患者完全缓解。准确的 AML 诊断依赖于形态学，最初仅由细胞化学辅助。与急性淋巴细胞白血病 (ALL) 不同，至少在 1970 年代和 1980 年代，免疫表型对 AML 的诊断几乎没有帮助。可靠的细胞遗传学的出现改变了 AML 的整个预后前景。通过核型分析，可以对不同组的 AML 进行分类和分层，以进行各种治疗。借助细胞上抗原标记的免疫表型鉴定，独特的突变分析是进一步分类 AML 患者的重大进步。所有这些进步都是随着对肿瘤负荷重要性的理解——称为微小残留病 (MRD)——对 AML 患者的管理变得至关重要。MRD 的疗效在过去十年中迅速发展，从特异性 10^-3免疫表型到 10 ^-4聚合酶链反应（PCR），仅适用于一些 AML 患者，最后到 10 ^-5甚至 10 ^-6具有下一代测序 (NGS) 非凡灵敏度的细胞。所有这些进步都促进了个性化医疗的概念，这导致了可以准确用于特定诊断亚型的靶向药物的出现。可以准确地预测和测量响应。此类靶向药物现已成为 AML 管理的基石，可提高疗效并显着降低毒性。本综述的重点是 AML 中研究最充分的靶向药物之一：FMS 样酪氨酸激酶 3 (FLT3) 抑制剂，它影响了 AML 的预后和治疗。本综述选择性地详细讨论了 FLT3 抑制剂，作为其他已获批准的新兴靶向药物以及目前正在开发的靶向药物的模型。