Blood:决定AML老年患者经venetoclax联合化疗预后的分子特征!

2020-01-14 QQY MedSci原创

中心点:适应性耐药可能是多克隆的,并与双等位基因TP53异常或激酶激活有关,特别是FLT3-ITD。NPM1突变与以venetoclax为基础的联合化疗后的良好的生存前景和持久的分子缓解相关。摘要:BCL-2抑制剂venetoclax联合低甲基化制剂或低剂量的阿糖孢苷是治疗老年或不适宜的急性髓系白血病(AML)患者的重要新疗法。DiNardo等人分析了81位采用以venetoclax为基础的联合化

中心点:

适应性耐药可能是多克隆的,并与双等位基因TP53异常或激酶激活有关,特别是FLT3-ITD。

NPM1突变与以venetoclax为基础的联合化疗后的良好的生存前景和持久的分子缓解相关。

摘要:

BCL-2抑制剂venetoclax联合低甲基化制剂或低剂量的阿糖孢苷是治疗老年或不适宜的急性髓系白血病(AML)患者的重要新疗法。DiNardo等人分析了81位采用以venetoclax为基础的联合化疗的患者,来分析持久缓解、缓解后复发(适应性耐药)或难治性疾病(原发性耐药)的分子相关性。

高缓解率和持久缓解与NPM1或IDH2突变(mut)典型相关,而延长的分子缓解与NPM1 mut相关。对以venetoclax为基础的联合方案原发性和适应性耐药病例最常见的特征是克隆获得或富集、信号通路激活(如FLT3或RAS)或双等位基因干扰TP53。

单细胞研究强调了在某些病例中的肿瘤内耐药机制的多克隆性。在原发难治性的病例中,研究人员发现在一个治疗周期内,白血病克隆的时间间隔发生了异质性的分歧变化,突出了AML治疗性进化的动态和快速发生。

功能性研究显示,FLT3-ITD获得或TP53缺失对以venetoclax和细胞毒性为基础的治疗产生了交叉耐药。

综上所述,本研究强调了采用venetoclax联合治疗的AML患者临床预后相关的分子决定因素。

原始出处:

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    2020-08-16 canlab
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    2020-01-15 thm112988

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