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在多发性髓瘤中第二次HDCT后低频率PPM1D基因突变的患病率上升

Katja Seipel¹, Nuria Z Veglio², Henning Nilius³

¹Department for Biomedical Research, University of Bern, 3008 Bern, Switzerland.

Current issues in molecular biology

|August 28, 2024

概括

周围血液细胞中PPM1D基因的体质突变与移植后多发性骨髓瘤患者的较差结果有关. PPM1D突变表明自主干细胞移植后的无进展和整体存活率较低.

科学领域:

血液学血液学血液学
癌症遗传学癌症遗传学
分子生物学分子生物学

背景情况:

多发性骨髓瘤 (MM) 的治疗包括免疫化疗 (ICT),高剂量化疗 (HDCT),自身干细胞移植 (ASCT) 和维持疗法.
复发是常见的,需要进一步的治疗线路,包括新型免疫疗法.
周围血液细胞的体质突变,例如PPM1D基因,与血液恶性瘤的不良结果有关.

研究的目的:

调查多发性骨髓瘤患者外周血液细胞中PPM1D基因突变的患病率.
评估PPM1D突变与HDCT/ASCT后的临床结果之间的相关性.

主要方法:

来自75名多发性骨髓瘤患者的周围血液细胞在HDCT/ASCT后缓解后被分析为PPM1D基因突变.
确定了突变的存在和变异性等位基因频率 (VAF).
在PPM1D突变 (PPM1Dmut) 和野生类型 (PPM1Dwt) 组之间比较了无进展生存 (PFS) 和总生存 (OS).

主要成果:

在第一个HDCT/ASCT后的1.3%患者和第二个HDCT/ASCT后的7.3%患者中发现了切断PPM1D突变,VAF为0.01-0.05.
在PPM1Dmut患者中,结果明显较差:PFS中位数为15个月,而PFS中位数为37个月 (p=0.0002).
与PPM1Dwt患者 (156个月) 相比,PPM1Dmut患者 (36个月) 的中位 OS 也减少了 (p=0.001).

结论:

在外围血液细胞中发生PPM1D基因突变的发生与多发性髓瘤中ASCT后的劣质临床结果相关.
在接受ASCT的MM患者中,PPM1D突变可以作为治疗反应和生存的预测生物标志物.

关键词:

自体干细胞移植 (ASCT)克隆性血液形成 (CH)多发性骨髓瘤 (MM) 是一种下一代测序 (NGS) 是指下一代的测序.蛋白质酸酶Mg/Mn依赖的1D (PPM1D) 是一种蛋白质酸酶.野生类型的p53诱导的酸酶1 (Wip1)

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