RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
新诊断慢性髓性白血病患者中遗传学改变与缓解率的相关性
英文原题：The association of genetic alterations with response rate in newly diagnosed chronic myeloid leukemia patients.
查看英文原题
The association of genetic alterations with response rate in newly diagnosed chronic myeloid leukemia patients.
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中文摘要
遗传差异可能与慢性髓性白血病（CML）患者对酪氨酸激酶抑制剂（TKI）的应答相关。本研究在慢性期CML患者中比较TKI治疗的快速应答者与缓慢应答者［治疗6个月时BCR/ABL1国际标准化值分别为≤0.1%和>0.1%］的遗传改变。研究分析了单核苷酸多态性（SNP）、全基因组关联研究及全网络关联研究（NetWAS）。来自16家机构的72例患者入组并接受尼洛替尼治疗。基因集分析发现，与多种先天免疫细胞分化、增殖和活性相关的通路存在遗传改变。NetWAS分析显示，自然杀伤（NK）细胞相关基因PTPRCAP、BLNK、HCK、ARHGEF11、GPR183、TRPV2、SHKBP1和CD2在尼洛替尼快速与缓慢应答者间存在显著差异。
然而，SNP分析未发现与应答显著相关的遗传改变。综上，TKI应答速度与免疫细胞相关通路的遗传改变有关，尤其涉及NK细胞活性。这些结果提示，初诊时的先天免疫系统对CML患者的治疗应答具有重要作用。
展开英文摘要原文
Genetic differences may be associated with the response to tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML). In this study, we identified genetic alterations between rapid and slow responders (BCR/ABL1 International Scale at 6 months: 0. 1 % vs. > 0. 1 %) of TKI treatment in chronic phase CML patients.
Our analyses involved single nucleotide polymorphism (SNP), a Genome Wide Association Study and a Network-wide Association Study (NetWAS). Seventy-two patients from 16 institutions were enrolled and treated with a TKI, nilotinib.
Gene Set Analysis identified genetic alterations in pathways related to the differentiation, proliferation, and activity of various innate immune cells. The NetWAS analysis found that genes associated with natural killer (NK) cells (PTPRCAP, BLNK, HCK, ARHGEF11, GPR183, TRPV2, SHKBP1, CD2) showed significant differences between rapid and slow responders of nilotinib.
However, we found no significantly different genetic alterations according to the response in the SNP analysis.
In conclusion, we found that rapidity of response to TKI was associated with pathway-associated genetic alterations in immune cells, particularly with respect to NK cell activity. These results suggested that the innate immune system at initial diagnosis had an important role in treatment response in patients with CML.
论文信息
- 作者
- Park H、Kang S、Kim I、Kim S、Kim HJ、Shin DY、Kim DY、Lee KH
- 第一作者单位
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.South Korea
- 通讯作者单位
- Department of Bioinformatics and Life Science, Soongsil University, Seoul, Republic of Korea. Electronic address: sskimb@ssu.ac.kr.South Korea
- 文献类型
- 非美国政府资助研究
- 期刊
- Leukemia research2022 Mar
- 原文标识
- PubMed 35101736 · DOI 10.1016/j.leukres.2022.106791