Institut National de la Santé et de la Recherche Médicale, U1035 Bordeaux, France.
Université de Bordeaux, 33076 Bordeaux, France.
Int J Mol Sci. 2019 Jul 12;20(14):3429. doi: 10.3390/ijms20143429.
Acute myeloid leukemia (AML) is a myeloid malignancy carrying a heterogeneous molecular panel of mutations participating in the blockade of differentiation and the increased proliferation of myeloid hematopoietic stem and progenitor cells. The historical "3 + 7" treatment (cytarabine and daunorubicin) is currently challenged by new therapeutic strategies, including drugs depending on the molecular landscape of AML. This panel of mutations makes it possible to combine some of these new treatments with conventional chemotherapy. For example, the FLT3 receptor is overexpressed or mutated in 80% or 30% of AML, respectively. Such anomalies have led to the development of targeted therapies using tyrosine kinase inhibitors (TKIs). In this review, we document the history of TKI targeting, FLT3 and several other tyrosine kinases involved in dysregulated signaling pathways.
急性髓系白血病（AML）是一种髓系恶性肿瘤，携带参与分化阻滞和髓系造血干细胞和祖细胞过度增殖的异质性分子突变面板。历史上的“3+7”治疗（阿糖胞苷和柔红霉素）目前受到新的治疗策略的挑战，包括依赖 AML 分子特征的药物。该突变面板使得可以将其中一些新的治疗方法与常规化疗相结合。例如，FLT3 受体在 AML 中分别过度表达或突变 80%或 30%。这些异常导致了使用酪氨酸激酶抑制剂（TKI）的靶向治疗的发展。在这篇综述中，我们记录了 TKI 靶向、FLT3 和其他几个参与失调信号通路的酪氨酸激酶的历史。
