Genetic features and clinical outcomes of patients with isolated and comutated DDX41-mutated myeloid neoplasms.
Genetic features and clinical outcomes of patients with isolated and comutated DDX41-mutated myeloid neoplasms.
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DOI：
10.1182/bloodadvances.2021005738
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发表时间：
2022-01-25
期刊：
影响因子：
7.5
通讯作者：
Al-Kali A
中科院分区：
文献类型：
--
作者：
Alkhateeb HB;Nanaa A;Viswanatha D;Foran JM;Badar T;Sproat L;He R;Nguyen P;Jevremovic D;Salama ME;Greipp P;Gangat N;Tefferi A;Litzow MR;Mangaonkar AA;Shah MV;Patnaik M;Al-Kali A
分离和突变的DDX41髓系肿瘤具有不同的特点。DDX41突变的AML具有与核心结合因子AML相当的相对有利的结果。DDX41突变(胚系和体细胞)与晚发性骨髓增生异常综合征/急性髓系白血病(MDS/AML)相关。在2016年世界卫生组织的分类修订中，具有种系易感性的髓系肿瘤(MN)被确定为一个独特的类别，包括具有种系DDX41突变的MN。我们回顾分析了33例DDX41突变(MDDX41)患者的分子表现和临床特征。我们在32名患者中发现了14个不同的致病DDX41变种，在9名患者中发现了8个未知意义的DDX41变种。5名患者(16%)有第二个DDX41体细胞突变p.R525H，13名患者(40%)在其他基因中至少有一个额外的致癌共突变。确诊时的中位年龄为66岁，以男性为主(72%)，大多数患者的细胞遗传学正常(91%)。两年总生存率(OS)为86%，6例(21%)MDS/AML患者的造血功能相对保留，未作进一步干预。与预后更好的亚型[t(8；21)，n=27和inv(16)，n=40]的AML患者相比，我们队列中的mDDX41患者表现出相似的有利OS。我们的研究强调，mDDX41-MN患者通常病程缓慢，mDDX41-AML的OS与风险较高的AML相似。
Isolated and comutated DDX41 myeloid neoplasms have different characteristics. DDX41-mutated AML has a relatively favorable outcome comparable to core binding factor AML. DDX41 mutations (germline and somatic) are associated with late onset myelodysplastic syndromes/acute myeloid leukemia (MDS/AML). Myeloid neoplasms (MN) with germline predisposition was identified as a distinct category in the 2016 WHO classification revision, including MN with germline DDX41 mutation. We retrospectively analyzed the molecular findings and clinical characteristics of thirty-three DDX41-mutated (mDDX41) patients at our institution. We identified 14 distinct pathogenic DDX41 variants in 32 patients and 8 DDX41 variants of unknown significance (VUS) in 9 patients. Five (16%) patients had a second DDX41 somatic mutation p.R525H and 13 (40%) had at least one additional oncogenic co-mutation in other genes. The median age at the time of diagnosis was 66 years, with male predominance (72%) and the majority of patients had normal cytogenetics (91%). Two-year overall survival (OS) was 86% and 6 (21%) MDS/AML patients with relatively preserved hematopoietic function were observed without further intervention. In comparison to AML patients with prognostically more favorable subtypes [t(8;21), n=27 and inv(16), n=40], mDDX41 patients in our cohort showed similarly favorable OS. Our study highlights that mDDX41-MN patients often have an indolent course and mDDX41-AML has comparable OS to favorable-risk AML.
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