High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia
High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia
复制标题
DOI：
10.1182/blood-2003-09-3074
复制
发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Inaba, T
中科院分区：
文献类型：
--
作者：
Harada, H;Harada, Y;Inaba, T
在低分化急性髓性白血病（AML，MO）和放射相关和治疗相关骨髓增生异常综合征（MDS）或AML中，报告了AML 1/RUNX1基因体细胞获得性点突变的高发生率。在这些疾病中鉴定的AML1突变绝大多数位于氨基（N）末端区域，特别是在DNA结合Runt同源结构域。在这份报告中，我们发现AML 1点突变26例（23.6%）的110例难治性贫血伴原始细胞过多（RAEB），RAEB转化（RAEBt），AML后MDS（定义为这3种疾病类别MDS/AML）。其中，9例（8.2%）突变发生在羧基（C）末端区域，仅见于MDS/AML，与散发性MDS/AML密切相关。所有伴有AML-1突变的MDS/AML患者均表达野生型AML-1蛋白，并且与无AMI-1突变的患者相比，其预后显著更差。大多数AML 1突变体失去了反式激活潜力，无论其DNA结合潜力。这些数据表明，AML1点突变是MDS/AML的主要驱动力之一，这些突变可能代表了一个独特的临床病理遗传实体。(C)2004年，美国血液学会。
A high incidence of somatically acquired point mutations in the AML1/RUNX1 gene has been reported in poorly differentiated acute myeloid leukemia (AML, MO) and in radiation-associated and therapy-related myelodysplastic syndrome (MDS) or AML. The vast majority of AML1 mutations identified in these diseases were localized in the amino (N)-terminal region, especially in the DNA-binding Runt homology domain. In this report, we show that AML1 point mutations were found in 26 (23.6%) of 110 patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEBt), and AML following MDS (defined these 3 disease categories as MDS/AML). Among them, 9 (8.2%) mutations occurred in the carboxy (C)terminal region, which were exclusively found in MDS/AML and were strongly correlated with sporadic MDS/AML. All patients with MDS/AML with an AML1 mutation expressed wild-type AML1 protein and had a significantly worse progno-sis than those without AMI-1 mutations. Most AML1 mutants lost trans-activation potential, regardless of their DNA binding potential. These data suggested that AML1 point mutation is one of the major driving forces of MDS/AML, and these mutations may represent a distinct clinicopathologic-genetic entity. (C) 2004 by The American Society of Hematology.