title: Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos.
abstract: BACKGROUND
  The best current xenograft model of multiple myeloma (MM) in immune-deficient non-obese diabetic/severe-combined immunodeficient mice is costly, animal maintenance is complex and several weeks are required to establish engraftment and study drug efficacy. More practical in vivo models may reduce time and drug development cost. We recently described a rapid low-cost xenograft model of human blood malignancies in pre-immune turkey. Here, we report application of this system for studying MM growth and the preclinical assessment of anticancer therapies.
  
  
  METHODS
  Cell lines and MM patient cells were injected intravenously into embryonic veins on embryonic day 11 (E11). Engraftment of human cells in haematopoietic organs was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry and circulating free light chain.
  
  
  RESULTS
  Engraftment was detected after 1 week in all embryos injected with cell lines and in 50% of those injected with patient cells. Injection of bortezomib or lenalinomide 48 h after cell injection at therapeutic levels that were not toxic to the bone marrow dramatically reduced MM engraftment.
  
  
  CONCLUSIONS
  The turkey embryo provides a practical, xenograft system to study MM and demonstrates the utility of this model for rapid and affordable testing therapeutics in vivo. With further development, this model may enable rapid, inexpensive personalised drug screening.
authors: Department of Hematology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, Tel Aviv Israel.
authors: Y
authors: Y
authors: Farnoushi
authors: M
authors: M
authors: Cipok
authors: S
authors: S
authors: Kay
authors: H
authors: H
authors: Jan
authors: A
authors: A
authors: Ohana
authors: E
authors: E
authors: Naparstek
authors: R S
authors: RS
authors: Goldstein
authors: V R
authors: VR
authors: Deutsch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004625:Embryo, Nonmammalian; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D011719:Pyrazines / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014422:Turkeys; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib