High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome
High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome
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DOI：
10.1038/sj.leu.2404135
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发表时间：
2006-04-01
期刊：
影响因子：
11.4
通讯作者：
Maruyama, Y
中科院分区：
文献类型：
--
作者：
Okamoto, M;Shichishima, T;Maruyama, Y
为了阐明再生障碍性贫血（AA）和骨髓增生异常综合征（MDS）患者与阵发性睡眠性血红蛋白尿症（PNH）患者相比磷脂酰肌醇聚糖A类基因（PIG-A）突变的一些特征，我们研究了7例AA、8例MDS和11例PNH日本患者的CD 59（-）粒细胞和CD 48（-）单核细胞的PIG-A突变。AA和MDS患者中PIG-A基因最常见的碱基或类型异常分别是碱基取代或错义突变，PNH患者中分别是缺失或移码突变。在所有AA和MDS患者的糖基磷脂酰肌醇阴性细胞中发现了几种PIG-A突变，其中大部分在统计学上是轻微的，但不是所有PNH患者。除例5外，未发现AA和MDS患者的CD 59（-）粒细胞和/或CD 48（-）单核细胞在临床病程中常见的PIG-A突变，而5例AA和5例MDS患者的粒细胞和单核细胞PIG-A突变不同。我们的研究结果表明，有一些特点的PIG-A突变的AA和MDS患者相比，PNH患者和几个较小的PNH克隆在这些患者中随机发生在临床过程中。这部分解释了AA或MDS向PNH的间歇性转化。
To clarify some characteristics of phosphatidylinositol glycan-class A gene (PIG-A) mutations in aplastic anemia (AA) and myelodysplastic syndrome (MDS) patients compared with those in paroxysmal nocturnal hemoglobinuria (PNH) patients, we investigated PIG-A mutations in CD59(-) granulocytes and CD48(-) monocytes from seven AA, eight MDS, and 11 PNH Japanese patients. The most frequent base or type abnormalities of the PIG-A gene in AA and MDS patients were base substitutions or missense mutations, respectively, and deletions or frameshift mutations, respectively, in PNH patients. Several PIG-A mutations, most of which were statistically minor, were found in glycosylphosphatidylinositol-negative cells from all AA and MDS patients but not from all PNH patients. However, the common PIG-A mutations during the clinical course between CD59(-) granulocytes and/or CD48(-) monocytes from each AA or MDS patient, except for Case 5, were not found. PIG-A mutations were different between the granulocytes and monocytes from five AA and five MDS patients. Our results indicate that there were some characteristics of PIG-A mutations in AA and MDS patients compared with PNH patients and that several minor PNH clones in these patients occurred at random during the clinical course. This partly explains the transformation of AA or MDS to PNH at intervals.