Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos

被引:5
作者
Farnoushi, Y. [1 ,2 ]
Cipok, M. [1 ]
Kay, S. [1 ]
Jan, H. [1 ,2 ]
Ohana, A. [2 ]
Naparstek, E. [1 ]
Goldstein, R. S. [2 ]
Deutsch, V. R. [1 ]
机构
[1] Tel Aviv Univ, Dept Hematol, Tel Aviv Sourasky Med Ctr, Sackler Fac Med, IL-62439 Tel Aviv, Israel
[2] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel
关键词
multiple myeloma; turkey embryo xenograft; drug response; CELLS; MODEL; THALIDOMIDE; ENGRAFTMENT; BORTEZOMIB; MICE; INHIBITION; ADHESION; AML;
D O I
10.1038/bjc.2011.445
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. CONCLUSION: 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. British Journal of Cancer (2011) 105, 1708-1718. doi:10.1038/bjc.2011.445 www.bjcancer.com
引用
收藏
页码:1708 / 1718
页数:11
相关论文
共 31 条
[1]  
Borset M, 2000, BLOOD, V96, P2528
[2]  
Boulland Jean-Luc, 2010, J Vis Exp, DOI 10.3791/2071
[3]   A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma [J].
Chauhan, Dharminder ;
Singh, Ajita V. ;
Aujay, Monette ;
Kirk, Christopher J. ;
Bandi, Madhavi ;
Ciccarelli, Bryan ;
Raje, Noopur ;
Richardson, Paul ;
Anderson, Kenneth C. .
BLOOD, 2010, 116 (23) :4906-4915
[4]   Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis [J].
Dalloul, Rami A. ;
Long, Julie A. ;
Zimin, Aleksey V. ;
Aslam, Luqman ;
Beal, Kathryn ;
Blomberg, Le Ann ;
Bouffard, Pascal ;
Burt, David W. ;
Crasta, Oswald ;
Crooijmans, Richard P. M. A. ;
Cooper, Kristal ;
Coulombe, Roger A. ;
De, Supriyo ;
Delany, Mary E. ;
Dodgson, Jerry B. ;
Dong, Jennifer J. ;
Evans, Clive ;
Frederickson, Karin M. ;
Flicek, Paul ;
Florea, Liliana ;
Folkerts, Otto ;
Groenen, Martien A. M. ;
Harkins, Tim T. ;
Herrero, Javier ;
Hoffmann, Steve ;
Megens, Hendrik-Jan ;
Jiang, Andrew ;
de Jong, Pieter ;
Kaiser, Pete ;
Kim, Heebal ;
Kim, Kyu-Won ;
Kim, Sungwon ;
Langenberger, David ;
Lee, Mi-Kyung ;
Lee, Taeheon ;
Mane, Shrinivasrao ;
Marcais, Guillaume ;
Marz, Manja ;
McElroy, Audrey P. ;
Modise, Thero ;
Nefedov, Mikhail ;
Notredame, Cedric ;
Paton, Ian R. ;
Payne, William S. ;
Pertea, Geo ;
Prickett, Dennis ;
Puiu, Daniela ;
Qioa, Dan ;
Raineri, Emanuele ;
Ruffier, Magali .
PLOS BIOLOGY, 2010, 8 (09)
[5]  
Dazzi F, 2000, Hematol J, V1, P307, DOI 10.1038/sj.thj.6200051
[6]   International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders [J].
Dispenzieri, A. ;
Kyle, R. ;
Merlini, G. ;
Miguel, J. S. ;
Ludwig, H. ;
Hajek, R. ;
Palumbo, A. ;
Jagannath, S. ;
Blade, J. ;
Lonial, S. ;
Dimopoulos, M. ;
Comenzo, R. ;
Einsele, H. ;
Barlogie, B. ;
Anderson, K. ;
Gertz, M. ;
Harousseau, J. L. ;
Attal, M. ;
Tosi, P. ;
Sonneveld, P. ;
Boccadoro, M. ;
Morgan, G. ;
Richardson, P. ;
Sezer, O. ;
Mateos, M. V. ;
Cavo, M. ;
Joshua, D. ;
Turesson, I. ;
Chen, W. ;
Shimizu, K. ;
Powles, R. ;
Rajkumar, S. V. ;
Durie, B. G. M. .
LEUKEMIA, 2009, 23 (02) :215-224
[7]  
FEOZUPPARDI FJ, 1992, BLOOD, V80, P2843
[8]   Improved engraftment of human acute myeloid leukemia progenitor cells in beta 2-microglobulin-deficient NOD/SCID mice and in NOD/SCID mice transgenic for human growth factors [J].
Feuring-Buske, M ;
Gerhard, B ;
Cashman, J ;
Humphries, RK ;
Eaves, CJ ;
Hogge, DE .
LEUKEMIA, 2003, 17 (04) :760-763
[9]   Bortezomib and thalidomide, a steroid free regimen in newly diagnosed patients with multiple myeloma [J].
Ghosh, Nilanjan ;
Ye, Xiaobu ;
Ferguson, Anna ;
Huff, Carol Ann ;
Borrello, Ivan .
BRITISH JOURNAL OF HAEMATOLOGY, 2011, 152 (05) :593-599
[10]   Engraftment of human blood malignancies to the turkey embryo: A robust new in vivo model [J].
Grinberg, Igor ;
Reis, Arbel ;
Ohana, Avivit ;
Taizi, Moran ;
Cipok, Michal ;
Tavor, Sigal ;
Rund, Deborah ;
Deutsch, Varda R. ;
Goldstein, Ronald S. .
LEUKEMIA RESEARCH, 2009, 33 (10) :1417-1426