文章：

BRAF V600E突变在早期多发性骨髓瘤中：对广谱药物反应良好，与预后无关

BRAF V600E mutation in early-stage multiple myeloma: good response to broad acting drugs and no relation to prognosis

原文发布日期：2015-03-20

DOI: 10.1038/bcj.2015.24

类型: Original Article

开放获取: 是

英文摘要：

In this study, we analyzed the prevalence and clone size of BRAF V600E mutation in 209 patients with multiple myeloma and related the results to clinical phenotype, response and survival. Biopsies were screened for BRAF V600E by allele-specific real-time PCR (AS-PCR). Positive results were confirmed by immunohistochemistry, Sanger sequencing and, in three patients from whom we had stored purified myeloma cells, whole-exome sequencing. Eleven patients (5.3%) were BRAF V600E mutation positive by AS-PCR and at least one other method. The fraction of mutated cells varied from 4 to 100%. BRAF V600E-positive patients had no characteristic clinical phenotype except for significantly higher levels of serum creatinine (125 versus 86 μmol/l) Seven of eleven patients responded with at least very good partial response to alkylators, immunomodulatory agents or proteasome inhibitors. Progression-free and overall survival were similar in patients with and without the mutation. By this integrated approach, we found that patients with BRAF V600E mutation responded very well to broad acting drugs and there was no relation to prognosis in early-stage myeloma. In particular, a large mutated cell fraction did not correlate with aggressive disease.

摘要翻译： 

在本研究中，我们分析了209例多发性骨髓瘤患者中BRAF V600E突变的患病率及克隆规模，并将结果与临床表现、治疗反应及生存期进行关联分析。通过等位基因特异性实时PCR（AS-PCR）对活检组织进行BRAF V600E筛查，阳性结果均经免疫组织化学、桑格测序验证，其中3例患者还采用储存的纯化骨髓瘤细胞进行了全外显子组测序确认。经AS-PCR及至少一种其他方法验证，共有11例（5.3%）患者为BRAF V600E突变阳性，突变细胞比例介于4%-100%之间。除血清肌酐水平显著升高（125 μmol/L 对 86 μmol/L）外，BRAF V600E阳性患者未表现出特征性临床表现。11例患者中有7例对烷化剂、免疫调节剂或蛋白酶体抑制剂治疗达到至少非常好的部分缓解。无论是否存在该突变，患者的无进展生存期和总生存期均无显著差异。通过这种综合分析方法，我们发现BRAF V600E突变患者对广谱抗癌药物反应良好，且在早期骨髓瘤中该突变与预后无关。特别值得注意的是，较高的突变细胞比例与侵袭性疾病进展无相关性。

原文链接：

BRAF V600E mutation in early-stage multiple myeloma: good response to broad acting drugs and no relation to prognosis