Kralovics Robert, Teo Soon-Siong, Li Sai, Theocharides Alexandre, Buser Andreas S, Tichelli Andre, Skoda Radek C
Department of Research, Experimental Hematology, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.
Blood. 2006 Aug 15;108(4):1377-80. doi: 10.1182/blood-2005-11-009605. Epub 2006 May 4.
An acquired gain-of-function mutation in the Janus kinase 2 (JAK2-V617F) is frequently found in patients with myeloproliferative disorders (MPDs). To test the hypothesis that JAK2-V617F is the disease-initiating mutation, we examined whether all cells of clonal origin carry the JAK2-V617F mutation. Using allele-specific polymerase chain reaction (PCR) assays for the JAK2 mutation and for the X-chromosomal clonality markers IDS and MPP1, we found that the percentage of granulocytes and platelets with JAK2-V617F was often markedly lower than the percentage of clonal granulocytes determined by IDS or MPP1 clonality assays in female patients. Using deletions of chromosome 20q (del20q) as an autosomal, X-chromosome-independent clonality marker, we found a similar discrepancy between the percentage of cells carrying JAK2-V617F and del20q. Our results suggest that in a proportion of patients with MPDs, JAK2-V617F occurs on the background of clonal hematopoiesis caused by a somatic mutation in an as-yet-unknown gene.
在骨髓增殖性疾病（MPD）患者中经常发现Janus激酶2（JAK2-V617F）的获得性功能获得性突变。为了检验JAK2-V617F是疾病起始突变这一假设，我们检查了所有克隆起源的细胞是否携带JAK2-V617F突变。使用针对JAK2突变以及X染色体克隆性标志物IDS和MPP1的等位基因特异性聚合酶链反应（PCR）检测，我们发现女性患者中携带JAK2-V617F的粒细胞和血小板百分比通常明显低于通过IDS或MPP1克隆性检测确定的克隆性粒细胞百分比。使用20号染色体缺失（del20q）作为常染色体、不依赖X染色体的克隆性标志物，我们发现在携带JAK2-V617F的细胞百分比和del20q之间存在类似差异。我们的结果表明，在一部分MPD患者中，JAK2-V617F发生在由一个尚未明确的基因中的体细胞突变引起的克隆性造血背景上。
