Human B Lymphomas Reveal Their Secrets Through Genetic Mouse Models
| Autor: | Mossadegh-Keller, Noushin, Brisou, Gabriel, Beyou, Alicia, Nadel, Bertrand, Roulland, Sandrine |
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| Přispěvatelé: | Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), DUMENIL, Anita |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
B-Lymphocytes
epigenetic modifier mutations Lymphoma B-Cell [SDV]Life Sciences [q-bio] Immunology germinal center (GC) Mice Transgenic Review diffuse large B cell lymphoma (DLBCL) Germinal Center Translocation Genetic Epigenesis Genetic Gene Expression Regulation Neoplastic [SDV] Life Sciences [q-bio] Disease Models Animal Mice follicular lymphoma (FL) Monitoring Immunologic hemic and lymphatic diseases Biomarkers Tumor genetically engineered mouse (GEMs) Animals Humans Genetic Predisposition to Disease Disease Susceptibility |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Frontiers, 2021, 12, ⟨10.3389/fimmu.2021.683597⟩ Frontiers in Immunology, 2021, 12, ⟨10.3389/fimmu.2021.683597⟩ |
| ISSN: | 1664-3224 |
| Popis: | International audience; Lymphomas are cancers deriving from lymphocytes, arising preferentially in secondary lymphoid organs, and represent the 6th cancer worldwide and the most frequent blood cancer. The majority of B cell Non-Hodgkin lymphomas (B-NHL) develop from germinal center (GC) experienced mature B cells. GCs are transient structures that form in lymphoid organs in response to antigen exposure of naive B cells, and where B cell receptor (BCR) affinity maturation occurs to promote B cell differentiation into memory B and plasma cells producing high-affinity antibodies. Genomic instability associated with the somatic hypermutation (SHM) and class-switch recombination (CSR) processes during GC transit enhance susceptibility to malignant transformation. Most B cell differentiation steps in the GC are at the origin of frequent B cell malignant entities, namely Follicular Lymphoma (FL) and GCB diffuse large B cell lymphomas (GCB-DLBCL). Over the past decade, large sequencing efforts have provided a great boost in the identification of candidate oncogenes and tumor suppressors involved in FL and DLBCL oncogenesis. Mouse models have been instrumental to accurately mimic in vivo lymphoma-specific mutations and interrogate their normal function in the GC context and their oncogenic function leading to lymphoma onset. The limited access of biopsies during the initiating steps of the disease, the cellular and (epi)genetic heterogeneity of individual tumors across and within patients linked to perturbed dynamics of GC ecosystems make the development of genetically engineered mouse models crucial to decipher lymphomagenesis and disease progression and eventually to test the effects of novel targeted therapies. In this review, we provide an overview of some of the important genetically engineered mouse models that have been developed to recapitulate lymphoma-associated (epi)genetic alterations of two frequent GC-derived lymphoma entities: FL and GCB-DLCBL and describe how those mouse models have improved our knowledge of the molecular processes supporting GC B cell transformation. |
| Databáze: | OpenAIRE |
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