Hematology Service, University Hospital La Fe, Valencia, Spain.
Curr Opin Oncol. 2009 Nov;21(6):594-600. doi: 10.1097/CCO.0b013e32833118fd.
The management of acute myeloid leukemia (AML) presents significant challenges, and there remains a need for new therapies with greater efficacy and better tolerability than existing treatments. An improved understanding of the genetic and molecular changes underlying AML can help both to guide treatment strategies and to predict clinical outcomes, thereby enabling more precise decision-making regarding the optimal treatment strategy for individual patients.
The tyrosine kinase receptor FLT3 plays an important role in the survival and proliferation of blasts, and approximately 25% of patients with AML have mutations in the FLT3 gene. This protein is therefore an obvious therapeutic target in AML. Amongst recently developed tyrosine kinase inhibitors of FLT3, lestaurtinib and midostaurin are two orally bioavailable agents that have shown encouraging activity, both preclinically and in relapsed AML, and are now in phase III clinical trials. These agents are also being tested in combination with conventional chemotherapy.
Oral FLT3 inhibitors offer a hope of improved treatment outcomes for patients with relapsed and newly diagnosed AML.
急性髓系白血病（AML）的治疗存在重大挑战，因此仍需要新的治疗方法，这些方法在疗效和耐受性方面要优于现有治疗方法。对 AML 潜在遗传和分子变化的深入了解，有助于指导治疗策略和预测临床结局，从而能够针对个体患者的最佳治疗策略做出更精确的决策。
酪氨酸激酶受体 FLT3 在白血病细胞的存活和增殖中发挥着重要作用，大约 25%的 AML 患者存在 FLT3 基因突变。因此，该蛋白是 AML 的一个明显的治疗靶点。在最近开发的 FLT3 酪氨酸激酶抑制剂中，lestaurtinib 和 midostaurin 是两种口服生物利用的药物，它们在复发和新诊断的 AML 中均显示出令人鼓舞的活性，目前正在进行 III 期临床试验。这些药物也正在与常规化疗联合进行测试。
口服 FLT3 抑制剂为复发和新诊断的 AML 患者提供了改善治疗结果的希望。
