Lee Eun-Ju, Zeidan Amer M
Section of Hematology, Department of Internal Medicine, Yale University, 333 Cedar Street, PO Box 208028, New Haven, CT, USA.
Expert Rev Hematol. 2015 Apr;8(2):155-8. doi: 10.1586/17474086.2015.1016905. Epub 2015 Feb 19.
Evaluation of: Bejar R, Lord A, Stevenson K, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood 2014 Oct 23;124(17):2705-12. Patients with myelodysplastic syndromes (MDS) have clinically variable courses even within the same prognostic subgroups. Although hypomethylating agents (HMAs) have been shown to improve outcomes in patients with high-risk MDS, many patients do not derive benefit. There is an urgent clinical need to identify patients with low probability of benefiting from HMAs but no reliable clinical predictors or biomarkers have been discovered to date. Although some recurrent molecular mutations in MDS carry independent prognostic value, their ability to predict benefit from HMAs is not clear. Here, we discuss an important article in which sequencing from samples of 213 patients identified recurrent mutations associated with response to HMAs. Although an important step in the right direction, the clinical implications of these findings are far from optimal and identification of biomarkers that can reliably predict benefit from HMAs and other therapies in patients with MDS remains a top clinical and a research priority.
贝哈尔·R、洛德·A、史蒂文森·K等人。TET2突变预测骨髓增生异常综合征患者对低甲基化药物的反应。《血液》2014年10月23日；124(17):2705 - 2712。骨髓增生异常综合征（MDS）患者即使在相同的预后亚组中临床病程也存在差异。尽管低甲基化药物（HMAs）已被证明可改善高危MDS患者的预后，但许多患者并未从中获益。临床上迫切需要识别出从HMAs治疗中获益可能性低的患者，但迄今为止尚未发现可靠的临床预测指标或生物标志物。虽然MDS中的一些复发性分子突变具有独立的预后价值，但其预测从HMAs治疗中获益的能力尚不清楚。在此，我们讨论一篇重要文章，其中对213例患者的样本进行测序，确定了与对HMAs反应相关的复发性突变。尽管这是朝着正确方向迈出的重要一步，但这些发现的临床意义远未达到最佳状态，识别能够可靠预测MDS患者从HMAs及其他治疗中获益的生物标志物仍然是临床和研究的首要任务。
