The Polymorphisms in LNK Gene Correlated to the Clinical Type of Myeloproliferative Neoplasms.
The Polymorphisms in LNK Gene Correlated to the Clinical Type of Myeloproliferative Neoplasms.
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LNK基因多态性与骨髓增生性肿瘤临床类型的相关性
DOI：
10.1371/journal.pone.0154183
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhu P
中科院分区：
文献类型：
--
作者：
Chen Y;Fang F;Hu Y;Liu Q;Bu D;Tan M;Wu L;Zhu P
目的LNK是一种负性调节JAK/STAT细胞信号通路的适配蛋白。本研究观察LNK基因变异与骨髓增生性肿瘤(MPN)临床类型的关系。方法收集285例MPN患者，其中原发性血小板增多症(ET)154例，真性红细胞增多症(PV)76例，原发性骨髓纤维化(PMF)19例，慢性粒细胞白血病(CML)36例。并以93例健康人作为正常对照。用等位基因特异性聚合酶链式反应检测JAK2基因V617F突变，用RT-PCR检测bcr/abl1融合基因，用聚合酶链式反应-测序法检测LNK基因编码外显子及其侧翼序列的突变和变异。结果8例LNK中发现A300V、V402M和R415H错义突变，包括ET(4例，均合并JAK2-V617F突变)、PV(2例，1例合并JAK2-V617F突变)、PMF(1例，合并JAK2-V617F突变)和CML(1例，合并BCR/ABL1融合基因)。MPN患者LNK中rs3184504、rs111340708和rs78894077三个SNPs的基因型和等位基因频率在MPN患者和对照组之间差异有统计学意义。Rs3184504(T/C，外显子2)T等位基因(p.262W)和TT等位基因在ET、PV和PMF中常见(P<；0.01)，C等位基因(p.262R)和CC等位基因在CML中常见(P<；0.01)。Rs78894077(T/C，外显子1)的T等位基因(p.242S)常见于ET(P<0.05)。Rs111340708(TGGGGx5/TGGGGx4)等位基因在ET、PMF和CML中少见(P<；0.01)。结论JAK2-V617F突变可在部分MPN患者中发现LNK基因突变。LNK基因的几个多态性可能影响MPN的临床类型或遗传易感性。
Objective LNK is an adapter protein negatively regulating the JAK/STAT cell signaling pathway. In this study, we observed the correlation between variation in LNK gene and the clinical type of myeloproliferative neoplasms (MPN). Methods A total of 285 MPN cases were recruited, including essential thrombocythemia (ET) 154 cases, polycythemia vera (PV) 76 cases, primary myelofibrosis (PMF) 19 cases, and chronic myeloid leukemia (CML) 36 cases. Ninety-three healthy individuals were used as normal controls. V617F mutation in JAK2 was identified by allele-specific PCR method, RT-PCR was used for the detection of BCR/ABL1 fusion gene, and mutations and variations in coding exons and their flanking sequences of LNK gene were examined by PCR-sequencing. Results Missense mutations of A300V, V402M, and R415H in LNK were found in 8 patients including ET (4 cases, all combined with JAK2-V617F mutation), PV (2 cases, one combined with JAK2-V617F mutation), PMF (one case, combined with JAK2-V617F mutation) and CML (one case, combined with BCR/ABL1 fusion gene). The genotype and allele frequencies of the three SNPs (rs3184504, rs111340708 and rs78894077) in LNK were significantly different between MPN patients and controls. For rs3184504 (T/C, in exon2), the T allele (p.262W) and TT genotype were frequently seen in ET, PV and PMF (P<0.01), and C allele (p.262R) and CC genotype were frequently seen in CML (P<0.01). For rs78894077 (T/C, in exon1), the T allele (p.242S) was frequently found in ET (P<0.05). For rs111340708 (TGGGGx5/TGGGGx4, in intron 5), the TGGGG x4 allele was infrequently found in ET, PMF and CML(P<0.01). Conclusion Mutations in LNK could be found in some of MPN patients in the presence or absence of JAK2-V617F mutation. Several polymorphisms in LNK gene may affect the clinical type or the genetic predisposition of MPN.