Tumor-specific transcript variants of cyclin D1 in mantle cell lymphoma and multiple myeloma with chromosome 11q13 abnormalities
Tumor-specific transcript variants of cyclin D1 in mantle cell lymphoma and multiple myeloma with chromosome 11q13 abnormalities
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DOI：
10.1016/j.exphem.2020.02.004
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发表时间：
2020-04-01
影响因子：
2.6
通讯作者：
Kuroda, Junya
中科院分区：
文献类型：
--
作者：
Chinen, Yoshiaki;Tsukamoto, Taku;Kuroda, Junya
细胞周期蛋白D1（CCND 1）过表达是套细胞淋巴瘤（MCL）和多发性骨髓瘤（MM）染色体11 q13异常的早期和统一的致癌事件。在此，我们报告了新发现的CCND 1基因在MCL和MM细胞染色体11 q13异常的转录变体。这些转录变体，命名为CCND1.tv.，CCND 1的5 ′-非翻译区（5 ′-UTR）覆盖了CCND 1的全长编码区，偶尔还包含一个新的外显子。CCND1.tv的网站。在具有染色体易位t（11;14）（q13;q32）的患者来源的原代MCL或MM细胞中特异性可检测到，但在t（11;14）阴性细胞中不能检测到。CCND1.tv.不同的患者和细胞系。CCND1.tv的介绍。导致HEK 293细胞中正常大小的CCND 1蛋白表达增加。此外，通过雷帕霉素或血清饥饿的mTOR抑制减少了CCND 1. tv.在HEK 293细胞中，CCND 1. tv.受mTOR途径调节。我们的研究结果表明，CCND1.tv.可能有助于了解MCL和11 q13异常MM的发病机制。(C)2020 ISEH -血液学和干细胞学会。爱思唯尔公司出版。All rights reserved.
Cyclin D1 (CCND1) overexpression is an early and unifying oncogenic event in mantle cell lymphoma (MCL) and multiple myeloma (MM) with chromosome 11q13 abnormalities. Herein, we report newly discovered transcript variants of the CCND1 gene in MCL and MM cells with chromosome 11q13 abnormalities. These transcript variants, designated CCND1.tv., covered the full-length coding region of CCND1 with longer 5'-untranslated regions (5'-UTRs) of CCND1 and occasionally contained a novel exon. CCND1.tv . was specifically detectable in patient-derived primary MCL or MM cells with chromosomal translocation t(11;14)(q13;q32), but not in t(11;14)-negative cells. The lengths of the 5'-UTR sequences of CCND1.tv. differed among patients and cell lines. Introduction of CCND1.tv. led to increased expression of normal-sized CCND1 protein in HEK293 cells. Furthermore, mTOR inhibition by rapamycin or serum starvation reduced ectopic expression of CCND1.tv.-derived CCND1 protein, but not 5'-UTR less CCND1-derived CCND1 protein in HEK293 cells, suggesting that the protein expression of CCND1.tv. is regulated by the mTOR pathway. Our results suggest that the aberrant expression of CCND1.tv. may contribute to the understanding of the pathogenesis of MCL and MM with 11q13 abnormalities. (C) 2020 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.