Patnaik Mrinal M
a Division of Hematology , Mayo Clinic , Rochester , MN , USA.
Leuk Lymphoma. 2018 Oct;59(10):2273-2286. doi: 10.1080/10428194.2017.1399312. Epub 2017 Nov 22.
Activating mutations in FMS-like tyrosine kinase 3 (FLT3), including internal tandem duplications (ITDs) and tyrosine kinase domain (TKD) mutations, are common in patients with acute myeloid leukemia (AML). FLT3-ITD is a negative prognostic factor that remains prognostically relevant even after intensive chemotherapy and/or stem cell transplant. FLT3 testing was historically viewed as being purely prognostic; however, with the advent of FLT3 inhibitors, it will likely be seen as both prognostic and predictive. The multikinase inhibitor midostaurin, in combination with chemotherapy, is the first targeted agent to significantly prolong survival in patients with newly diagnosed FLT3-mutated AML and was recently approved by health authorities. Recently, the European LeukemiaNet recommended FLT3 testing (both TKD and ITD) for all patients with AML, with results required within 3 days. The need for optimized, multigene platform testing incorporating FLT3 mutations will increase as knowledge of interactions between FLT3 and other myeloid-relevant mutations grows.
FMS样酪氨酸激酶3（FLT3）的激活突变，包括内部串联重复（ITD）和酪氨酸激酶结构域（TKD）突变，在急性髓系白血病（AML）患者中很常见。FLT3-ITD是一种不良预后因素，即使在强化化疗和/或干细胞移植后仍具有预后相关性。FLT3检测在历史上被视为纯粹的预后指标；然而，随着FLT3抑制剂的出现，它可能会被视为既具有预后意义又具有预测意义。多激酶抑制剂米哚妥林与化疗联合使用，是首个能显著延长新诊断的FLT3突变型AML患者生存期的靶向药物，最近已获卫生当局批准。最近，欧洲白血病网建议对所有AML患者进行FLT3检测（包括TKD和ITD），并要求在3天内出结果。随着对FLT3与其他髓系相关突变之间相互作用的了解不断增加，对纳入FLT3突变的优化多基因平台检测的需求也会增加。
