Schlenk R F, Döhner K, Döhner H
Klinik für Innere Medizin III, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, 89081, Ulm.
Internist (Berl). 2013 Feb;54(2):171-8. doi: 10.1007/s00108-012-3154-y.
Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.
急性髓系白血病（AML）是一种基因异质性疾病。基因诊断已成为疾病分类、预后评估和预测初始检查的重要组成部分。越来越多有前景的分子靶向治疗药物可供使用。个体化治疗策略的一个先决条件是进行快速的治疗前分子筛查，包括融合基因PML-RARA、RUNX1-RUNX1T1和CBFB-MYH11，以及NPM1、FLT3和CEBPA基因的突变。有前景的新治疗方法包括在急性早幼粒细胞白血病中使用全反式维甲酸和三氧化二砷联合治疗，在核心结合因子AML中使用强化化疗与KIT抑制剂联合治疗，在伴有FLT3突变的AML中使用FLT3抑制剂，以及在细胞遗传学低风险和中风险患者中使用吉妥珠单抗奥唑米星治疗。随着下一代测序技术的出现，预计将发现新的治疗靶点。这些见解将导致AML治疗的进一步个体化。
