Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 41, Issue 6, Pages 2047-2056Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2012.1634
Keywords
leukemia; intra-bone marrow transplantation; firefly luciferase; bioluminescent imaging; animal model
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Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2011-0015112]
- National Research Foundation of Korea [2011-0015112] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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In vivo leukemia mouse models are usually generated by intraperitoneal (IP) or intravenous (IV) injection of leukemia cells. However, the pattern of leukemia development observed can be inconsistent. This study investigated injection directly into bone marrow [intra-bone marrow transplantation (IBMT)], the natural microenvironment of leukemia. A bioluminescent imaging-based leukemia animal model has been established by direct injection of a bioluminescent leukemia cells (CCRF-CEM/fLuc) into NOD/SCID mouse tibia bone marrow and compared with models established by IP and IV routes. The comparison revealed that a bioluminescent in vivo leukemia model established via IBMT could recapitulate leukemia more faithfully and facilitate improved quantification of leukemia engraftment kinetics with a wider range of bioluminescent intensity than IP or IV. IBMT of bioluminescent leukemic cells allowed quantification of dose-dependent responses to anti-leukemic drugs, thus validating this model as a potential preclinical anti-leukemic drug screening system. IBMT-leukemia cells isolated from peripheral blood of the model mice and then injected into new recipients successfully established a second generation IBMT in vivo model and demonstrated the reproducibility of the model. Bioluminescent imaging-based analysis of this IBMT-leukemia model could provide a means for the comprehensive evaluation of treatment responses with enhanced sensitivity in preclinical studies.
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