TP53 mutations are associated with mutated MYD88 and CXCR4, and confer an adverse outcome in Waldenstrom macroglobulinaemia
TP53 mutations are associated with mutated MYD88 and CXCR4, and confer an adverse outcome in Waldenstrom macroglobulinaemia
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DOI：
10.1111/bjh.15560
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发表时间：
2019-01-01
影响因子：
6.5
通讯作者：
Xu, Lian
中科院分区：
文献类型：
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作者：
Gustine, Joshua N.;Tsakmaklis, Nicholas;Xu, Lian
关于瓦尔登斯特伦巨球蛋白血症（WM）中的TP53突变知之甚少。我们通过下一代测序评估了265例WM患者的TP 53突变，并通过桑格测序验证了结果。在6例（2例中心点6%）患者中鉴定并验证了影响DNA结合结构域的TP53突变。所有六个都是MYD88和CXCR4突变的。伊布替尼在携带所有三种突变的患者中显示出活性。中位随访时间为18个月，2例（33%）双等位基因TP 53失活患者死于疾病进展。TP53突变在WM中罕见，并且与MYD88和CXCR4突变相关。具有TP53突变的WM患者显示对伊鲁替尼的应答。
Little is known about TP53 mutations in Waldenstrom Macroglobulinaemia (WM). We evaluated 265 WM patients for TP53 mutations by next-generation sequencing, and validated the findings by Sanger sequencing. TP53 mutations were identified and validated in 6 (2 center dot 6%) patients that impacted the DNA-binding domain. All six were MYD88- and CXCR4-mutated. Ibrutinib showed activity in patients carrying all three mutations. With a median follow-up of 18 months, 2 (33%) with biallelic TP53 inactivation died of progressive disease. TP53 mutations are rare in WM, and associate with MYD88 and CXCR4 mutations. WM patients with TP53 mutations show response to ibrutinib.