Schlenk Richard F, Döhner Konstanze
Department of Internal Medicine III, University Hospital of Ulm, Germany.
Curr Opin Hematol. 2009 Mar;16(2):98-104. doi: 10.1097/MOH.0b013e3283257adb.
In recent years, new molecular markers have emerged as significant prognostic parameters and as potential targets for molecularly targeted therapy in acute myeloid leukemia (AML). However, prognostic markers cannot guide the decision for a specific treatment, as they are associated with a differential outcome regardless of the given treatment. In contrast, predictive markers indicate a treatment benefit in patients that are characterized through these markers. Thus, predictive markers can guide clinical decision-making.
In young adults, mutations of the nucleophosmin (gene 9NPM1) in the absence of concurrent FLT3-internal tandem duplication (ITD) (FLT3-ITD) have impressive prognostic and, beyond prognostication, predictive properties. This NPM1/FLT3-ITD genotype predicts equivalent favorable outcome after intensive chemotherapy and allogeneic stem cell transplantation, whereas in the absence of this marker clinical outcome was significantly improved after an allogeneic transplantation. In addition, within a retrospective study performed on older adults, the same genotype predicted a significantly improved outcome if all-trans retinoic acid was added to intensive chemotherapy.
The discovery of new prognostic and predictive markers has increased our understanding of leukemogenesis and this may lead to improved prognostication and, more important, to novel genotype-specific treatment strategies.
近年来，新的分子标志物已成为急性髓系白血病（AML）重要的预后参数和分子靶向治疗的潜在靶点。然而，预后标志物不能指导特定治疗的决策，因为无论给予何种治疗，它们都与不同的预后相关。相比之下，预测性标志物表明具有这些标志物特征的患者能从治疗中获益。因此，预测性标志物可指导临床决策。
在年轻成年人中，核仁磷酸蛋白（基因9NPM1）突变且无同时发生的FLT3内部串联重复（ITD）（FLT3-ITD）具有令人瞩目的预后特性，且除预后外还具有预测特性。这种NPM1/FLT3-ITD基因型预测强化化疗和异基因干细胞移植后有同等良好的预后，而在缺乏该标志物的情况下，异基因移植后临床结局显著改善。此外，在一项针对老年人的回顾性研究中，相同的基因型预测如果在强化化疗中加入全反式维甲酸，结局会显著改善。
新的预后和预测性标志物的发现增进了我们对白血病发生的理解，这可能会改善预后，更重要的是，带来新的基因型特异性治疗策略。
