title: Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4.
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.
authors.affiliation: Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mirandola
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Yu
authors.forename: Marjorie R
authors.initials: MR
authors.lastname: Jenkins
authors.forename: Raffaella
authors.initials: R
authors.lastname: Chiaramonte
authors.forename: Everardo
authors.initials: E
authors.lastname: Cobos
authors.forename: Constance M
authors.initials: CM
authors.lastname: John
authors.forename: Maurizio
authors.initials: M
authors.lastname: Chiriva-Internati
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger
chemical_list: D054758:A Kinase Anchor Proteins; C485479:Akap4 protein, mouse; D018398:Homeodomain Proteins; D053631:Interleukin Receptor Common gamma Subunit; D012333:RNA, Messenger; C064658:RAG-1 protein