Animal Models of Multiple Myeloma Bone Disease.

Ladan Mashouri,Carol A Morris,Syed Hassan Mehdi,Sana Nafees,Donghoon Yoon,Syed Jafar Mehdi

doi:10.3389/fgene.2021.640954

Ladan Mashouri, Carol A Morris + Show 4 more

Open Access

https://doi.org/10.3389/fgene.2021.640954

Copy DOI

Abstract

Multiple myeloma (MM) is a clonal B-cell disorder characterized by the proliferation of malignant plasma cells (PCs) in the bone marrow, the presence of monoclonal serum immunoglobulin, and osteolytic lesions. It is the second most common hematological malignancy and considered an incurable disease despite significant treatment improvements. MM bone disease (MMBD) is defined as the presence of one or more osteolytic bone lesions or diffused osteoporosis with compression fracture attributable to the underlying clonal PC disorder. MMBD causes severe morbidity and increases mortality. Cumulative evidence shows that the interaction of MM cells and bone microenvironment plays a significant role in MM progression, suggesting that these interactions may be good targets for therapy. MM animal models have been developed and studied in various aspects of MM tumorigenesis. In particular, MMBD has been studied in various models, and each model has unique features. As the general features of MM animal models have been reviewed elsewhere, the current review will focus on the features of MMBD animal models.

Highlights

Multiple myeloma (MM) is a plasma cell (PC) malignancy that represents an accumulation of terminally differentiated monoclonal plasma cells (PCs) in the bone marrow (BM) (Katz, 2010)
MM is preceded by a premalignant disease known as monoclonal gammopathy of undetermined significance (MGUS) (Weiss et al, 2009; Landgren et al, 2019)
During the progression of MGUS to MM, that complex genetic changes occur in the PCs, and changes in the BM microenvironment (BME) occur, including angiogenesis, immune suppression, and increasing bone resorption (Kyle and Rajkumar, 2004)

Summary

INTRODUCTION

Multiple myeloma (MM) is a plasma cell (PC) malignancy that represents an accumulation of terminally differentiated monoclonal PC in the bone marrow (BM) (Katz, 2010). Human Xenograft in NSG Mouse A variety of myeloma cell lines, JJN3 (Lawson et al, 2015b), OPM2 (Fuhler et al, 2012; Lawson et al, 2015b), U266 (Dewan et al, 2004; Miyakawa et al, 2004; Bartee et al, 2012a; Bartee et al, 2012b; Lawson et al, 2015b), RPMI-8226-Luc (Hurchla et al, 2013), MM.1S (Bartee et al, 2012a), HuNS1 (Bartee et al, 2012a), L363 (Udi et al, 2013), and KMM-1 (Dewan et al, 2004), as well as primary patient-derived MCs (Lawson et al, 2015b), have been administered to NSG mice, which results in classical features of MM including paraplegia, paraprotein in the serum, osteolytic lesions, and loss of trabecular bone. To test the effectiveness of antitumor and bone modulating drugs against human myeloma in vivo (Rabin et al, 2007; Fryer et al, 2013; Hurchla et al, 2013; Lawson et al, 2015b; Paton-Hough et al, 2019)

Limitations

Findings

CONCLUSION