Division of Haematology, Department of Medicine, The University of Hong Kong, Hong Kong, China.
Division of Haematology, Department of Medicine, The University of Hong Kong, Hong Kong, China..
Blood Rev. 2017 Nov;31(6):418-425. doi: 10.1016/j.blre.2017.08.001. Epub 2017 Aug 4.
Information arising from next generation sequencing of leukemia genome has shed important light on the heterogeneous and combinatorial driver events in acute myeloid leukemia (AML). It has also provided insight into its intricate signaling pathways operative in the disease pathogenesis. These have also become biomarkers and targets for therapeutic intervention. Emerging evidence from in vitro drug screening has demonstrated its potential value in predicting clinical drug responses in specific AML subtypes. However, the best culture conditions and readouts have yet to be standardized and the drugs included in these screening exercises frequently revised in view of the rapid emergence of new therapeutic agents in the oncology field. Testing of leukemia cell functions, including BCL2 profiling, has also been used to predict treatment response to conventional chemotherapy and hypomethylating agents as well as BCL2 antagonist in small patient cohorts. These platforms should be integrated into future clinical trials to develop personalized treatment of AML.
白血病基因组的下一代测序所产生的信息，为急性髓细胞白血病（AML）中的异质性和组合驱动事件提供了重要的启示。它还深入了解了其在疾病发病机制中复杂的信号通路。这些也已成为治疗干预的生物标志物和靶点。体外药物筛选的新证据表明，它在预测特定 AML 亚型的临床药物反应方面具有潜在价值。然而，最佳的培养条件和读数尚未标准化，并且鉴于肿瘤学领域新的治疗药物的快速出现，这些筛选中包含的药物经常被修订。白血病细胞功能的测试，包括 BCL2 分析，也被用于预测对常规化疗、低甲基化剂以及小患者队列中 BCL2 拮抗剂的治疗反应。这些平台应该整合到未来的临床试验中，以制定 AML 的个性化治疗方案。
