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多发性骨髓瘤中ABL基因扩增的证据及其治疗意义。

Evidence for ABL Amplification in Multiple Myeloma and Therapeutic Implications.

作者信息

Huang He, Zhou Shuping, Lin Hongdou, Guo Wenjian, Lin Ying, Yao Ronxin, He Licai, Yu Kang, Li Qian

机构信息

Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Department of Hematology, Ningbo Yinzhou Second Hospital, Ningbo, Zhejiang, China.

出版信息

J Oncol. 2022 Mar 15;2022:4112016. doi: 10.1155/2022/4112016. eCollection 2022.

DOI:10.1155/2022/4112016
PMID:35342415
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8941557/
Abstract

BACKGROUND

Cytogenetic abnormalities are considered initiating events in the pathogenesis of multiple myeloma (MM) and are assumed to be of clinical significance.

METHODS

Fluorescence in situ hybridization (FISH) was used to analyze chromosomal architecture in 101 patients with MM. We evaluated overall patient survival and assessed the cytotoxicity of imatinib against MM cells using a CCK8 assay.

RESULTS

ABL gene amplification was detected in 67 patients (66.3%). However, ABL gene amplification was not associated with clinical features, cytogenetic abnormalities (c-Myc amplification, IGH rearrangement, RB1 deletion, p53 deletion, or 1q21 amplification), or overall survival. ABL amplification in MM cell lines (LP-1 and U266) was revealed by FISH. Furthermore, the ABL protein was easily detectable in MM cell lines and some tumor cells by western blotting. A CCK8 assay indicated limited cytotoxicity of imatinib against MM cells.

CONCLUSIONS

Our study firstly discussed ABL gene amplification was prevalent in MM cells, and we believe that the ABL gene would potentially be a useful target in the treatment of combination strategy for MM with ABL amplification in the future.

摘要

背景

细胞遗传学异常被认为是多发性骨髓瘤(MM)发病机制中的起始事件,并被假定具有临床意义。

方法

采用荧光原位杂交(FISH)技术分析101例MM患者的染色体结构。我们评估了患者的总生存期,并使用CCK8法评估了伊马替尼对MM细胞的细胞毒性。

结果

67例患者(66.3%)检测到ABL基因扩增。然而,ABL基因扩增与临床特征、细胞遗传学异常(c-Myc扩增、IGH重排、RB1缺失、p53缺失或1q21扩增)或总生存期无关。FISH显示MM细胞系(LP-1和U266)中有ABL扩增。此外,通过蛋白质印迹法在MM细胞系和一些肿瘤细胞中很容易检测到ABL蛋白。CCK8法表明伊马替尼对MM细胞的细胞毒性有限。

结论

我们的研究首次探讨了ABL基因扩增在MM细胞中普遍存在,并且我们认为ABL基因在未来MM合并ABL扩增的联合治疗策略中可能是一个有用的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/147eeb0fade0/JO2022-4112016.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/5fe0df6e02d3/JO2022-4112016.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/52b53be07a15/JO2022-4112016.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/b2e830c2de07/JO2022-4112016.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/9e10af3a781c/JO2022-4112016.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/147eeb0fade0/JO2022-4112016.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/5fe0df6e02d3/JO2022-4112016.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/52b53be07a15/JO2022-4112016.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/b2e830c2de07/JO2022-4112016.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/9e10af3a781c/JO2022-4112016.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2a9/8941557/147eeb0fade0/JO2022-4112016.005.jpg

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Functional interplay between NF-κB-inducing kinase and c-Abl kinases limits response to Aurora inhibitors in multiple myeloma.NF-κB 诱导激酶和 c-Abl 激酶之间的功能相互作用限制了多发性骨髓瘤对 Aurora 抑制剂的反应。
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