Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin
Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin
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DOI：
10.1182/blood-2003-10-3471
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发表时间：
2004-06-01
期刊：
影响因子：
20.3
通讯作者：
Ueda, R
中科院分区：
文献类型：
--
作者：
Ding, F;Komatsu, H;Ueda, R
一个日本家系的家族性原发性血小板增多症（FET）的常染色体显性遗传方式。一个独特的点突变，丝氨酸505天冬酰胺505（Ser 505 Asn），被确定在跨膜结构域的c-MPL基因在所有的8个成员与血小板增多症，但没有在其他8个未受影响的成员在这个FET家族。表达突变型Asn 505的Ba/F3细胞获得了不依赖白细胞介素3（IL-3）的存活能力，而表达野生型Ser 505的细胞则没有。在不存在IL-3的情况下，在突变体Ba/F3细胞中观察到Mek 1/2和Stat 5 b的自主磷酸化。前者也被发现在血小板生成素的情况下，从受影响的个人衍生的血小板。这些结果表明Asn 505是关于细胞内信号传导和细胞存活的激活突变。这是第一次报告的FET来自一个显性阳性激活突变的c-MPL基因。(C)2004年，美国血液学会。
One Japanese pedigree of familial essential thrombocythemia (FET) inherited in an autosomal-dominant manner is presented. A unique point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin 3 (IL-3)-independent survival capacity, whereas those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET deriving from a dominant-positive activating mutation of the c-MPL gene. (C) 2004 by The American Society of Hematology.