High expression of activation-induced cytidine deaminase (AID) and splice variants is a distinctive feature of poor-prognosis chronic lymphocytic leukemia
High expression of activation-induced cytidine deaminase (AID) and splice variants is a distinctive feature of poor-prognosis chronic lymphocytic leukemia
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DOI：
10.1182/blood-2002-09-2906
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发表时间：
2003-06-15
期刊：
影响因子：
20.3
通讯作者：
Abruzzo, LV
中科院分区：
文献类型：
--
作者：
McCarthy, H;Wierda, WG;Abruzzo, LV
在慢性淋巴细胞白血病（CLL）中，对体细胞高突变的免疫球蛋白重链可变区进行分析，确定了2个预后亚群，突变亚群和未突变亚群。研究者假设未突变和突变的CLL分别来自生发前和生发后中心（GC） B细胞的恶性转化。另外，未突变的病例可能是由t细胞非依赖性抗原刺激的B细胞或无活性体细胞超突变的GC B细胞引起的。激活诱导胞苷脱氨酶（AID）是体细胞超突变的一种必需蛋白，在发生体细胞超突变的GC B细胞中表达。我们研究了20例CLL患者的AID mRNA表达。在8例中，我们检测到野生型AID mRNA和2个剪接变体的高表达；12例和5例正常外周血b细胞在标准条件下未检测到表达。在8例高表达AID的CLL病例中，有7例未突变，这表明该亚群可能来自gc经历过的具有失活体细胞超突变的B细胞，并可能预测预后。(血。101:4903 2003;4908)。
In chronic lymphocytic leukemia (CLL), analysis of immunoglobulin heavy chain variable regions for somatic hypermutation identifies 2 prognostic subsets, mutated and unmutated. Investigators have postulated that unmutated and mutated CLL arises from malignant transformation of pre- and post-germinal center (GC) B cells, respectively. Alternatively, unmutated cases may arise from B cells stimulated by T-cell-independent antigens or from GC B cells with inactive somatic hypermutation. Activation-induced cytidine deaminase (AID), a protein essential for somatic hypermutation, is expressed by GC B cells in which this process occurs. We investigated AID mRNA expression in 20 CLL cases. In 8 cases we detected high expression of wild-type AID mRNA and 2 splice variants; in 12 cases and 5 normal peripheral blood B-cell samples we detected no expression using standard conditions. Of 8 CLL cases that highly expressed AID, 7 were unmutated, suggesting that this subset may arise from GC-experienced B cells with inactive somatic hypermutation, and may predict prognosis. (Blood. 2003;101:4903-4908).