Toyama Kohtaro, Karasawa Masamitsu, Yokohama Akihiko, Mitsui Takeki, Uchiumi Hideki, Saitoh Takayuki, Handa Hiroshi, Murakami Hirokazu, Nojima Yoshihisa, Tsukamoto Norifumi
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Japan.
Intern Med. 2011;50(21):2557-61. doi: 10.2169/internalmedicine.50.5429. Epub 2011 Nov 1.
While the somatic mutation of Janus Kinase 2 (JAK2) and the thrombopoietin receptor (c-MPL) gene are thought to affect the pathogenesis of bcr/abl negative chronic myeloproliferative neoplasm (MPN), the relationship between the mutation and the clinical features remain obscure.
The mutation status of these genes in granulocytes, platelets, T-cells, and erythroid colonies (BFU-E) was obtained from 115 MPN patients, and then the clinical features of the MPN subtypes were compared.
The JAK2-V617F mutation was observed in three lineages of granulocytes, platelets, and BFU-E in almost all polycythemia vera (PV) and primary myelofibrosis (PMF) patients. In contrast, 68% of essential thrombocythemia (ET) patients have the JAK2-V617F mutation in at least one of the lineages, of which 70% of these patients have the JAK2-V617F mutation in three lineages; the remaining ET patients with the JAK2-V617F mutation only exhibited the mutation in one or two lineages. Further, the ET patients that exhibited the JAK2-V617F mutation in three lineages had higher WBC and granulocyte counts as compared to the ET patients that did not have the JAK2-V617F mutation or only had the mutation in one or two lineages. Concerning the MPL gene, two ET patients had the MPL-W515L gene mutation in their platelets, although the lineage of the JAK2-V617F mutation involved differed from case to case.
The progenitor cells that are involved with the JAK2-V617F mutation in MPNs are different in each subtype and this difference may also affect the clinical features of MPNs.
虽然认为Janus激酶2（JAK2）和血小板生成素受体（c-MPL）基因的体细胞突变会影响bcr/abl阴性慢性骨髓增殖性肿瘤（MPN）的发病机制，但该突变与临床特征之间的关系仍不清楚。
从115例MPN患者中获取粒细胞、血小板、T细胞和红系集落（BFU-E）中这些基因的突变状态，然后比较MPN各亚型的临床特征。
几乎所有真性红细胞增多症（PV）和原发性骨髓纤维化（PMF）患者的粒细胞、血小板和BFU-E三个谱系中均观察到JAK2-V617F突变。相比之下，68%的原发性血小板增多症（ET）患者至少在一个谱系中存在JAK2-V617F突变，其中70%的患者在三个谱系中存在JAK2-V617F突变；其余有JAK2-V617F突变的ET患者仅在一个或两个谱系中出现该突变。此外，与未发生JAK2-V617F突变或仅在一个或两个谱系中发生突变的ET患者相比，在三个谱系中出现JAK2-V617F突变的ET患者白细胞和粒细胞计数更高。关于MPL基因，两名ET患者血小板中存在MPL-W515L基因突变，尽管JAK2-V617F突变涉及的谱系因病例而异。
MPN中与JAK2-V617F突变相关的祖细胞在各亚型中有所不同，这种差异可能也会影响MPN的临床特征。
