Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma
Plasma cells (PCs) have an essential role in humoral immune response by secretion of antibodies, and represent the final stage of B lymphocytes differentiation. During this differentiation, the pre-plasmablastic stage is characterized by highly proliferative cells that start to secrete immunoglobuli...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/15/3755 |
| _version_ | 1797525727192547328 |
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| author | Laure Dutrieux Yea-Lih Lin Malik Lutzmann Raphaël Rodriguez Michel Cogné Philippe Pasero Jérôme Moreaux |
| author_facet | Laure Dutrieux Yea-Lih Lin Malik Lutzmann Raphaël Rodriguez Michel Cogné Philippe Pasero Jérôme Moreaux |
| author_sort | Laure Dutrieux |
| collection | DOAJ |
| description | Plasma cells (PCs) have an essential role in humoral immune response by secretion of antibodies, and represent the final stage of B lymphocytes differentiation. During this differentiation, the pre-plasmablastic stage is characterized by highly proliferative cells that start to secrete immunoglobulins (Igs). Thus, replication and transcription must be tightly regulated in these cells to avoid transcription/replication conflicts (TRCs), which could increase replication stress and lead to genomic instability. In this review, we analyzed expression of genes involved in TRCs resolution during B to PC differentiation and identified 41 genes significantly overexpressed in the pre-plasmablastic stage. This illustrates the importance of mechanisms required for adequate processing of TRCs during PCs differentiation. Furthermore, we identified that several of these factors were also found overexpressed in purified PCs from patients with multiple myeloma (MM) compared to normal PCs. Malignant PCs produce high levels of Igs concomitantly with cell cycle deregulation. Therefore, increasing the TRCs occurring in MM cells could represent a potent therapeutic strategy for MM patients. Here, we describe the potential roles of TRCs resolution factors in myelomagenesis and discuss the therapeutic interest of targeting the TRCs resolution machinery in MM. |
| first_indexed | 2024-03-10T09:17:57Z |
| format | Article |
| id | doaj.art-858f4db326614ffc8c6bbf34740fb44d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:17:57Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-858f4db326614ffc8c6bbf34740fb44d2023-11-22T05:27:21ZengMDPI AGCancers2072-66942021-07-011315375510.3390/cancers13153755Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple MyelomaLaure Dutrieux0Yea-Lih Lin1Malik Lutzmann2Raphaël Rodriguez3Michel Cogné4Philippe Pasero5Jérôme Moreaux6Institute of Human Genetics, UMR 9002 Centre National de la Recherche Scientifique, University of Montpellier, 34396 Montpellier, FranceInstitute of Human Genetics, UMR 9002 Centre National de la Recherche Scientifique, University of Montpellier, 34396 Montpellier, FranceInstitute of Human Genetics, UMR 9002 Centre National de la Recherche Scientifique, University of Montpellier, 34396 Montpellier, FranceChemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, 75005 Paris, FranceINSERM U1236, University of Rennes 1, Etablissement Français du Sang, 35000 Rennes, FranceInstitute of Human Genetics, UMR 9002 Centre National de la Recherche Scientifique, University of Montpellier, 34396 Montpellier, FranceInstitute of Human Genetics, UMR 9002 Centre National de la Recherche Scientifique, University of Montpellier, 34396 Montpellier, FrancePlasma cells (PCs) have an essential role in humoral immune response by secretion of antibodies, and represent the final stage of B lymphocytes differentiation. During this differentiation, the pre-plasmablastic stage is characterized by highly proliferative cells that start to secrete immunoglobulins (Igs). Thus, replication and transcription must be tightly regulated in these cells to avoid transcription/replication conflicts (TRCs), which could increase replication stress and lead to genomic instability. In this review, we analyzed expression of genes involved in TRCs resolution during B to PC differentiation and identified 41 genes significantly overexpressed in the pre-plasmablastic stage. This illustrates the importance of mechanisms required for adequate processing of TRCs during PCs differentiation. Furthermore, we identified that several of these factors were also found overexpressed in purified PCs from patients with multiple myeloma (MM) compared to normal PCs. Malignant PCs produce high levels of Igs concomitantly with cell cycle deregulation. Therefore, increasing the TRCs occurring in MM cells could represent a potent therapeutic strategy for MM patients. Here, we describe the potential roles of TRCs resolution factors in myelomagenesis and discuss the therapeutic interest of targeting the TRCs resolution machinery in MM.https://www.mdpi.com/2072-6694/13/15/3755multiple myelomatranscription replication conflictsR-loopsG-quadruplexesgenomic instabilitytumorigenesis |
| spellingShingle | Laure Dutrieux Yea-Lih Lin Malik Lutzmann Raphaël Rodriguez Michel Cogné Philippe Pasero Jérôme Moreaux Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma Cancers multiple myeloma transcription replication conflicts R-loops G-quadruplexes genomic instability tumorigenesis |
| title | Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma |
| title_full | Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma |
| title_fullStr | Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma |
| title_full_unstemmed | Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma |
| title_short | Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma |
| title_sort | transcription replication conflicts in tumorigenesis and their potential role as novel therapeutic targets in multiple myeloma |
| topic | multiple myeloma transcription replication conflicts R-loops G-quadruplexes genomic instability tumorigenesis |
| url | https://www.mdpi.com/2072-6694/13/15/3755 |
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