Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Division of Biostatistics and Bioinformatics, Johns Hopkins/Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Leuk Lymphoma. 2022 Aug;63(8):1942-1948. doi: 10.1080/10428194.2022.2057488. Epub 2022 Apr 4.
There are currently no known predictors of myelodysplastic syndrome (MDS)/myeloproliferative overlap neoplasm (MPN) patients' response to hypomethylating agents (HMA). Forty-three patients with MDS/MPN who were treated with HMA during chronic phase and had next-generation sequencing using the established 63-genes panel were identified. Complete and partial remission and marrow response were assessed based on the MDS/MPN International Working Group response criteria. On univariate analysis, younger age, higher number of mutations, and mutations in , , or were associated with no response. Multivariable analysis for modeling response were conducted least absolute shrinkage and selection operator logistic regression approach, and showed that mutations in , , or predict lack of HMA response. While limited by sample size, our findings suggest that genomic landscape can potentially identify MDS/MPN patients with lower likelihood of response to HMA.
目前尚无已知的预测指标可以预测骨髓增生异常综合征（MDS）/骨髓增生性重叠肿瘤（MPN）患者对低甲基化药物（HMA）的反应。在慢性期接受 HMA 治疗且使用已建立的 63 个基因 panel 进行下一代测序的 43 例 MDS/MPN 患者被确定。根据 MDS/MPN 国际工作组反应标准评估完全和部分缓解以及骨髓反应。在单因素分析中，年龄较小、突变数量较多以及 、 或 中的突变与无反应相关。使用最小绝对收缩和选择算子逻辑回归方法进行多变量分析以建立反应模型，结果表明 、 或 中的突变预测 HMA 反应缺乏。尽管受到样本量的限制，但我们的研究结果表明，基因组图谱可能可以识别对 HMA 反应可能性较低的 MDS/MPN 患者。
