Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome
Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome
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DOI：
10.1016/s0140-6736(08)61341-0
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发表时间：
2008-10-25
期刊：
影响因子：
168.9
通讯作者：
Izraeli, Shai
中科院分区：
文献类型：
--
作者：
Bercovich, Dani;Ganmore, Ithamar;Izraeli, Shai
背景唐氏综合征患儿发生急性巨核细胞白血病和急性淋巴细胞白血病的风险大大增加。唐氏综合征中的急性巨核细胞白血病的特征是GATA 1的体细胞突变。JAK/STAT（Janus激酶、信号转导子和转录激活子）通路的组成性激活发生在几种造血系统恶性疾病中。我们检验了JAK 2突变可能是与唐氏综合征相关的急性淋巴细胞白血病的常见分子事件的假设。方法对88例唐氏综合征相关急性淋巴细胞白血病和216例散发性急性淋巴细胞白血病的诊断性骨髓样本进行JAK 2 DNA突变分析。白血病、唐氏综合征相关的急性巨核细胞白血病和原发性血小板增多症。在小鼠造血祖细胞中研究了已识别突变的功能后果。结果体细胞获得性JAK 2突变在16例（18%）唐氏综合征相关急性淋巴细胞白血病患者中被确定。唯一一名非唐氏综合征相关白血病但JAK 2突变的患者具有等染色体21 q。JAK 2突变的儿童年龄更小（平均[SE]年龄4.5岁[0。86]8.6年[0] 59]，p
Background Children with Down's syndrome have a greatly increased risk of acute megakaryoblastic and acute lymphoblastic leukaemias. Acute megakaryoblastic leukaemia in Down's syndrome is characterised by a somatic mutation in GATA1. Constitutive activation of the JAK/STAT (Janus kinase and signal transducer and activator of transcription) pathway occurs in several haematopoietic malignant diseases. We tested the hypothesis that mutations in JAK2 might be a common molecular event in acute lymphoblastic leukaemia associated with Down's syndrome.Methods JAK2 DNA mutational analysis was done on diagnostic bone marrow samples obtained from 88 patients with Down's syndrome-associated acute lymphoblastic: leukaemia; and 216 patients with sporadic acute lymphoblastic: leukaemia, Down's syndrome-associated acute megakaryoblastic leukaemia, and essential thrombocythaemia. Functional consequences of identified mutations were studied in mouse haematopoietic progenitor cells.Findings Somatically acquired JAK2 mutations were identified in 16 (18%) patients with Down's syndrome-associated acute lymphoblastic leukaemia. The only patient with non-Down's syndrome-associated leukaemia but with a JAK2 mutation had an isochromosome 21q. Children with a JAK2 mutation were younger (mean [SE] age 4.5 years [0 . 86] vs 8.6 years [0 . 59], p