CSF3R基因变异与白血病 |
您所在的位置:网站首页 › csf3r基因突变会导致什么病 › CSF3R基因变异与白血病 |
![]() Characterization of the leukemogenic potential of distal cytoplasmic CSF3R truncation and missense mutations 引起白血病的远端细胞质CSF3R截短和错义突变 10.1038/leu.2017.126 2017-05-12, Article Abstract & Authors:展开 Abstract:收起An increasing number of variants of unknown significance are being identified in leukemia patients with the application of deep sequencing and these include CSF3R cytoplasmic mutations. Previous studies have demonstrated oncogenic potential of certain CSF3R truncation mutations prior to internalization motifs. However, the oncogenic potential of truncating the more distal region of CSF3R cytoplasmic domain as well as cytoplasmic missense mutations remains uncharacterized. Here we identified that CSF3R distal cytoplasmic truncation mutations (Q793-Q823) also harbored leukemogenic potential. Mechanistically, these distal cytoplasmic truncation mutations demonstrated markedly decreased receptor degradation, probably owing to loss of the de-phosphorylation domain (residues N818-F836). Furthermore, all truncations prior to Q823 demonstrated increased expression of the higher molecular weight CSF3R band, which is shown to be essential for the receptor surface expression and the oncogenic potential. We further demonstrated that sufficient STAT5 activation is essential for oncogenic potential. In addition, CSF3R K704A demonstrated transforming capacity due to interruption of receptor ubiquitination and degradation. In summary, we have expanded the region of the CSF3R cytoplasmic domain in which truncation or missense mutations exhibit leukemogenic capacity, which will be useful for evaluating the relevance of CSF3R mutations in patients and helpful in defining targeted therapy strategies.Leukemia advance online publication, 12 May 2017; doi:10.1038/leu.2017.126. First Authors:H Zhang Correspondence Authors:J W Tyner All Authors:H Zhang,A Reister Schultz,S Luty,A Rofelty,Y Su,S Means,D Bottomly,B Wilmot,S K McWeeney,J W Tyner |
今日新闻 |
推荐新闻 |
CopyRight 2018-2019 办公设备维修网 版权所有 豫ICP备15022753号-3 |