A bone paradigm challenging the standard model of myeloma oncogenesis. (April 2022)

• Record Type: Journal Article
• Authors: Capp, Jean-Pascal; Bataille, Régis
• Is Part Of: Critical reviews in oncology/hematology. Volume 172(2022)
• Publication Date: 2022-04
• Subjects: BME Bone Micro-Environment -- GD Gaucher Disease -- LBL Lytic Bone Lesion -- MGUS Monoclonal Gammopathy of Undetermined Significance -- MS-to-ObT Mesenchymal-Stromal to Osteoblast Transition -- MM Multiple Myeloma -- TiDiS tissue disruption-induced cellular stochasticity; Multiple myeloma -- Monoclonal gammopathy of undetermined significance -- Tissue disruption-induced cellular stochasticity (TiDiS) -- Bone inflamm'aging -- Bone marrow microenvironment -- Endosteal niche -- Mesenchymal-stromal to osteoblast transition (MS-to-ObT) -- Gaucher disease; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2022.103640
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: The standard model of multiple myeloma (MM) oncogenesis from monoclonal gammopathy of undetermined significance (MGUS) relies on genetic instability in the normal counterparts of MM cells. However, the importance of both MGUS-associated and MM-induced bone changes has been recently re-appraised, emphasizing the bone microenvironment (BME) as a tissue of significance. In this review, we propose that early BME alterations (bone senescence and inflammation, i.e., bone inflamm'aging) at the pre-MGUS stage could be causal, and not simply permissive, and creative of phenotypic instability and genetic alterations thanks to the concept of tissue disruption-induced cell stochasticity (TiDiS). This article offers a bone scenario challenging the chromosome-and-gene-centric standard model of MM oncogenesis. The high incidence of both MGUS and MM in Gaucher disease supports such a scenario. Graphical Abstract: ga1 Highlights: Multiple myeloma (MM) is generally considered as a purely genetics-driven disease. However alterations in the bone microenvironment (BME) intervene early by creating a permissive environment. We consider the potential initiating role of the disruption of the endosteal niche. Early BME alterations could be causal and creative of phenotypic instability and genetic alterations. Bone senescence and inflamm'aging could be at the origin of this early disruption.