Characterization Of Imaging-Enhanced Models Of Disseminated Multiple Myeloma

Multiple myeloma is a cancer of the plasma cells that is characterized by multiple localized lesions in the marrow, particularly of the spine, skull, and pelvis, although soft tissue lesions also occur. It is the second most common blood cancer, affecting approximately 45,000 people in the US. Most preclinical modeling of myeloma employs SC xenografts that mimic the less common plasmacytoma form of the disease. Systemic (IV) implants are also used, but studies typically are based on a single survival endpoint, limiting knowledge about the progression and response of the disease under treatment. In order to more quantitatively monitor disseminated disease progression and response to treatment, we have characterized two human (JJN3 and MM1S) and one murine (5TGM1) myeloma models that have been modified to express luciferase. All models were characterized by 100% tumor take rate and focal dissemination of the disease to the spine and skull that mimic clinical experience. These models showed individual and reproducible patterns of spread to other sites, and differed in their sensitivities to standards of care. Analysis of tumor doubling times, tumor titrations, luminescence-based growth delay, and survival all indicated that the bioluminescence signal was a reliable quantitative indicator of viable tumor burden, even under treatment with clinical standard of care agents. Luciferase labeling and the tight correlation between luminescence signal and viable tumor burden raises the possibility of differential real-time tracking of tumor progression and response at individual sites. Citation Format: Meridith Baugher, Jenifer Baranski, Deepa Balagurunathan, Christopher Bull, Noah Winchell, Darren Shaw, Erin Trachet, Deanne Lister, Patrick McConville, Wilbur R. Leopold. Characterization of imaging-enhanced models of disseminated multiple myeloma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3859. doi:10.1158/1538-7445.AM2013-3859