不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
JAK2 磷酸化 PBK/TOPK Tyr74 促进 Burkitt 淋巴瘤肿瘤生长
英文原题：Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth.
查看英文原题
Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth.
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中文摘要
Burkitt淋巴瘤（BL）以高侵袭性为特征，是非霍奇金淋巴瘤的一个亚组。尽管BL被认为是一种高度可治愈的疾病，尤其是对儿童而言，但不幸的是，一些患者仍然反应不佳。对BL的病因学和分子机制的理解仍然有限，靶向治疗仍然缺乏。在这里，我们发现T-LAK细胞衍生蛋白激酶（TOPK）和磷酸化Janus激酶2（p-JAK2）在BL患者组织中高表达。我们报道TOPK直接结合JAK2，并在Tyr74位点被JAK2磷酸化。组蛋白H3作为TOPK的下游靶点之一，在体内和体外也被磷酸化。此外，我们报道JAK2对TOPK Tyr74位点的磷酸化在BL细胞增殖中起重要作用，并在体内促进BL肿瘤发生。JAK2对TOPK Tyr74位点的磷酸化增强了TOPK的稳定性。总之，我们的结果表明JAK2/TOPK/组蛋白H3轴在BL细胞增殖和体内BL肿瘤发生中起关键作用。
展开英文摘要原文
Burkitt lymphoma (BL), which is characterized by high invasiveness, is a subgroup of non-Hodgkin lymphoma. Although BL is regarded as a highly curable disease, especially for children, some patients unfortunately still do not respond adequately. The understanding of the etiology and molecular mechanisms of BL is still limited, and targeted therapies are still lacking.
Here, we found that T-LAK cell-derived protein kinase (TOPK) and phosphorylated Janus kinase 2 (p-JAK2) are highly expressed in the tissues of BL patients.
We report that TOPK directly binds to and is phosphorylated at Tyr74 by JAK2. Histone H3, one of the downstream targets of TOPK, is also phosphorylated in vivo and in vitro.
Furthermore, we report that the phosphorylation of TOPK at Tyr74 by JAK2 plays a vital role in the proliferation of BL cells and promotes BL tumorigenesis in vivo. Phosphorylation of TOPK at Tyr74 by JAK2 enhances the stability of TOPK. Collectively, our results suggest that the JAK2/TOPK/histone H3 axis plays a key role in the proliferation of BL cells and BL tumorigenesis in vivo.
论文信息
- 作者
- Wang K、Wei J、Ma J、Jia Q、Liu Y、Chai J、Xu J、Xu T
- 第一作者单位
- State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Air Force Medical University, Xi'an, China.China
- 通讯作者单位
- State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Air Force Medical University, Xi'an, China. Electronic address: zhwang@fmmu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cancer letters2022 Sep 28
- 原文标识
- PubMed 35780928 · DOI 10.1016/j.canlet.2022.215812