一种挑战多发性骨髓瘤发生标准模型的骨细胞范式。

A bone paradigm challenging the standard model of myeloma oncogenesis.

机构信息

Toulouse Biotechnology Institute, INSA/University of Toulouse, CNRS, INRAE, 135, avenue de Rangueil, 31077 Toulouse, cedex 04, France.

University of Angers, School of Medecine, rue Haute de Reculée, 49045 Angers, cedex 01, France.

出版信息

Crit Rev Oncol Hematol. 2022 Apr;172:103640. doi: 10.1016/j.critrevonc.2022.103640. Epub 2022 Feb 18.

DOI:10.1016/j.critrevonc.2022.103640

PMID:35183697

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.

摘要

多发性骨髓瘤（MM）的标准发病模型源于意义未明的单克隆丙种球蛋白血症（MGUS），该模型依赖于 MM 细胞正常对应物的遗传不稳定性。然而，MGUS 相关和 MM 诱导的骨改变的重要性最近重新得到评估，强调了骨微环境（BME）作为一个重要的组织。在这篇综述中，我们提出在 pre-MGUS 阶段早期的 BME 改变（骨衰老和炎症，即骨炎症衰老）可能是因果关系，而不仅仅是允许和创造表型不稳定和遗传改变，这要归功于组织破坏诱导的细胞随机性（TiDiS）的概念。本文提供了一个挑战 MM 发病的染色体和基因中心标准模型的骨场景。戈谢病中 MGUS 和 MM 的高发生率支持这种情况。