Wu Ping, Weng Jianyu, Li Minming, Lu Zesheng, Deng Chengxin, Sun Qihui, Xu Ruohao, Geng Suxia, Du Xin
Department of Hematology, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences/Guangdong Provincial Geriatrics Institute Guangzhou, Guangdong, China.
Am J Transl Res. 2019 Jun 15;11(6):3651-3658. eCollection 2019.
The molecular determinants of the clinical response to Hypomethylating agents (HMAs) in patients with myelodysplastic syndromes (MDS) are unclear. We analyzed 84 adult patients with MDS who received hypomethylating agents (HMAs) and identified somatic mutations and their relationship to clinical response and survival. The results showed in the MDS patients with ASXL1 mutations,the most frequent co-occurring mutations were RUNX1 mutations, with a significant higher frequency of 43% compared to 17% in wild-type ASXL1 (P = 0.032). ASXL1 mutation demonstrated a significant negative overall response rate (8% vs. 29.4%, x = 5.228, P = 0.022), particularly when co-occurring with RUNX1 mutations (P = 0.008). And all patients with RUNX1 and ASXL1 mutations died with a shorter median overall survival of only 14 months (P = 0.002). Moreover, TP53 mutations were associated with unfavorable-risk cytogenetic changes, and responded well to HMAs, with the exception of one case with RUNX1 and ASXL1 gene mutation. In a word, RUNX1 mutations are frequently found in MDS patients with ASXL1-mutations, and Co-occurrence of RUNX1 and ASXL1 mutations are associated with poor response to HMAs and inferior survival.
骨髓增生异常综合征（MDS）患者对去甲基化药物（HMA）临床反应的分子决定因素尚不清楚。我们分析了84例接受去甲基化药物（HMA）治疗的成年MDS患者，确定了体细胞突变及其与临床反应和生存的关系。结果显示，在伴有ASXL1突变的MDS患者中，最常见的共发突变是RUNX1突变，其频率显著高于野生型ASXL1，分别为43%和17%（P = 0.032）。ASXL1突变显示出显著较低的总体缓解率（8%对29.4%，x = 5.228，P = 0.022），尤其是与RUNX1突变同时出现时（P = 0.008）。所有RUNX1和ASXL1突变的患者均死亡，中位总生存期仅为14个月，较短（P = 0.002）。此外，TP53突变与不良风险的细胞遗传学改变相关，并且对HMA反应良好，但有1例伴有RUNX1和ASXL1基因突变的患者除外。总之，RUNX1突变在伴有ASXL1突变的MDS患者中经常出现，RUNX1和ASXL1突变同时出现与对HMA反应不佳和生存较差相关。
