Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. While there have been many attempts to genetically recapitulate this disease in animal models, few reports describe plasma cell tumors that exhibit bone marrow involvement. We recently described a Bcl-X L transgenic mouse that developed polyclonal non-malignant B-cell expansions in the bone marrow and lymphoid organs. In this report, we describe induction of plasma cell tumors in littermate control and Bcl-XL transgenic mice with a retrovirus expressing v-Abl and c-Myc. Nearly 100% of the ABL-MYC-infected littermate control and Bcl-XL mice developed plasma cell tumors. There was no difference in tumor latency in young mice infected; however, following ABL-MYC infection, aged Bcl-XL mice demonstrated a median survival of 9 weeks, while littermate control mice demonstrated a median survival of 19 weeks. Interestingly, while both littermate control and Bcl-XL mice infected with the ABL-MYC retrovirus developed extramedullary plasma cell tumors, only the ABL-MYC-infected Bcl-XL mice, but not the ABL-MYC-infected littermate control mice, developed bone marrow plasma cell tumors with characteristic radiolucent bone lesions. Tumor cell populations were clonally related, and analysis of tumor immunoglobulin genes demonstrated evidence consistent with somatic hypermutation. This report implicates an unidentified role of Bcl-XL in bone marrow plasma cell tumor formation, as ABL-MYC retroviral infection only elicits bone marrow plasma cell tumors in mice that ectopically express Bcl-XL in their B- and plasma cells.
Bibliographical noteFunding Information:
Neoclone (Madison, WI, USA) for supplying ABL-MYC viral stocks, Cancer Center Histopathology Core, Linda Kiey, Sheri Kuslak, and Steve Wiesner (technical assistance), and David Largaespada (thoughtful discussion). M.L. supported by the NIH Lung Science Training Grant. M.K. supported by the 3M Science and Technology Fellowship. Project supported by the Leukemia Research Fund.
Copyright 2017 Elsevier B.V., All rights reserved.
- Multiple Myeloma