Open Access Highly Accessed Research article

Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4

Leonardo Mirandola12, Yuefei Yu1, Marjorie R Jenkins123, Raffaella Chiaramonte14, Everardo Cobos12, Constance M John5 and Maurizio Chiriva-Internati12*

Author Affiliations

1 Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA

2 The Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, USA

3 Departments of Internal Medicine and Obstetrics & Gynecology, Texas Tech University Health Sciences Center, Amarillo, TX, USA

4 Department of Medicine, Surgery and Dentistry, Università degli Studi di Milano, Milano, Italy

5 MandalMed, Inc., San Francisco, CA, USA

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BMC Cancer 2011, 11:394  doi:10.1186/1471-2407-11-394

Published: 16 September 2011

Abstract

Background

Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease.

Methods

Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4.

Results

Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45.

Conclusions

We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth in vivo and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies.