通过转录和遗传分析挑战功能性高风险髓瘤的概念
Sina Alexandra Beer1, David A Cairns2, Charlotte Pawlyn3
1Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, United Kingdom.
Blood
|August 20, 2025
概括
功能性高风险多发性骨髓瘤 (FHR MM) 经常被标准测试遗漏. 在诊断时进行全面的基因组和细胞遗传分析可以更好地确定患有早期复发风险的患者.
科学领域:
- 血液学
- 癌症学
- 遗传学
背景情况:
- 功能性高风险多发性骨髓瘤 (FHR) 呈现出意想不到的早期复发 (ER),尽管缺乏基线风险因素.
- 准确识别FHRMM是具有挑战性的,主要依赖于初步诊断评估和随后治疗的全面性.
研究的目的:
- 为了确定FHRMM的真实发生率.
- 评估结合细胞遗传和基因表达分析在识别FHRMM患者和预测结果方面的有效性.
主要方法:
- 来自英国NCRI Myeloma- XI试验的均治疗的可移植患者的分析.
- 对患者进行了国际骨髓瘤学会/国际骨髓瘤工作组 (IMS/ IMWG) 的高风险细胞遗传异常 (HRCA) 和SKY92基因表达高风险 (GEP- HR) 标记分析.
- 与风险分层相关的早期复发 (移植后18个月) 和长期存活率的评估.
主要成果:
- 在135名患者中,有25名 (18. 5%) 患有早期复发.
- 只有通过综合分析 (仅GEP-HR或单独的HR标志物) 确定了很大一部分早期复发,这凸显了标准方法的局限性.
- IMS/ IMWG-HR和GEP-HR的同时发生与非常短的整体存活率 (HR=13.1) 有关,其次仅有GEP-HR (HR=5. 1) 和IMS/ IMWG-HR (HR=3. 2).
结论:
- 标准诊断标准可能低估了FHRMM的发生率.
- 结合IMS/IMWG和GEP分析,可以更好地识别患有早期复发风险的患者.
- 在多发性骨髓瘤中,全面的基线分析对预先风险分层和个性化治疗策略至关重要.
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