Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma

Autor: Raphaël Rodriguez, Jérôme Moreaux, Yea-Lih Lin, Philippe Pasero, Malik Lutzmann, Laure Dutrieux, Michel Cogné
Přispěvatelé: Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Lapeyronie [Montpellier] (CHU), Université Paul-Valéry - Montpellier 3 (UPVM), INCa (Institut National du Cancer)Institut National du Cancer (INCA) France [PLBIO18-362 PIT-MM, PLBIO19-098 INCA_13832], ANR (the French National Research Agency) under the \'Investissements d'avenir\' program [ANR-16-IDEX-0006], ANR French National Research Agency (ANR) [2017-CE15-002401, ANR-18-CE15-0010-01], SIRIC Montpellier Cancer [INCaDGOS-Inserm_12553], Labex EpiGenMed, Institut Universitaire de France, Ligue Nationale Contre le Cancer LNCC, Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANR-16-IDEX-0006,MUSE,MUSE(2016), ANR-18-CE15-0010,PLASMADIFF-3D,Rôle de l'organisation tridimensionnelle et de la dynamique de la chromatine au cours de la différenciation plasmocytaire(2018), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC), Rodriguez, Raphaël, MUSE - - MUSE2016 - ANR-16-IDEX-0006 - IDEX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Rôle de l'organisation tridimensionnelle et de la dynamique de la chromatine au cours de la différenciation plasmocytaire - - PLASMADIFF-3D2018 - ANR-18-CE15-0010 - AAPG2018 - VALID
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Genome instability
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
Cancer Research
transcription replication conflicts
[SDV.CAN]Life Sciences [q-bio]/Cancer
Review
medicine.disease_cause
plasma cells
03 medical and health sciences
0302 clinical medicine
Immune system
[SDV.CAN] Life Sciences [q-bio]/Cancer
stomatognathic system
Transcription (biology)
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
medicine
Secretion
Gene
Multiple myeloma
RC254-282
biology
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
R-loops
medicine.disease
genomic instability
G-quadruplexes
3. Good health
Cell biology
multiple myeloma
tumorigenesis
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
biology.protein
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Antibody
Carcinogenesis
Zdroj: Cancers, Vol 13, Iss 3755, p 3755 (2021)
Cancers
Cancers, MDPI, 2021, 13 (15), pp.3755. ⟨10.3390/cancers13153755⟩
Cancers, 2021, 13 (15), pp.3755. ⟨10.3390/cancers13153755⟩
ISSN: 2072-6694
DOI: 10.3390/cancers13153755⟩
Popis: Simple Summary Multiple myeloma is a hematologic cancer characterized by the accumulation of malignant plasma cells in the bone marrow. It remains a mostly incurable disease due to the inability to overcome refractory disease and drug-resistant relapse. Oncogenic transformation of PC in multiple myeloma is thought to occur within the secondary lymphoid organs. However, the precise molecular events leading to myelomagenesis remain obscure. Here, we identified genes involved in the prevention and the resolution of conflicts between the replication and transcription significantly overexpressed during the plasma cell differentiation process and in multiple myeloma cells. We discussed the potential role of these factors in myelomagenesis and myeloma biology. The specific targeting of these factors might constitute a new therapeutic strategy in multiple myeloma. Abstract 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.
Databáze: OpenAIRE
Externí odkaz: