Affiliation:
1. Department of Hematology Zhongshan Hospital, Fudan University Shanghai China
2. Cancer Center Zhongshan Hospital, Fudan University Shanghai China
3. Department of Hematology Zhongshan Hospital (Xiamen), Fudan University Xiamen China
Abstract
SummaryPatients with multiple myeloma (MM) with chromosome 1q21 Gain (1q21+) are clinically and biologically heterogeneous. 1q21+ in the real world actually reflects the prognosis for gain/amplification of the CKS1B gene. In this study, we found that the copy number of prune exopolyphosphatase 1 (PRUNE1), located on chromosome 1q21.3, could further stratify the prognosis of MM patients with 1q21+. Using selected reaction monitoring/multiple reaction monitoring (SRM/MRM) analysis, liquid chromatography–tandem mass spectrometry (LC–MS/MS), transmission electron microscopy (TEM), confocal fluorescence microscopy, calculation of adenosine triphosphate (ATP), intracellular reactive oxygen species (ROS) and mitochondrial oxygen consumption rates (OCRs), we demonstrated for the first time that PRUNE1 promotes the proliferation and invasion of MM cells by stimulating purine metabolism, purine synthesis enzymes and mitochondrial functions, enhancing links between purinosomes and mitochondria. SOX11 was identified as a transcription factor for PRUNE1. Through integrated analysis of the transcriptome and proteome, CD73 was determined to be the downstream target of PRUNE1. Furthermore, it has been determined that dipyridamole can effectively suppress the proliferation of MM cells with high‐expression levels of PRUNE1 in vitro and in vivo. These findings provide insights into disease‐causing mechanisms and new therapeutic targets for MM patients with 1q21+.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Fujian Province
Natural Science Foundation of Shanghai Municipality
Cited by
2 articles.
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