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Article

Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles

  • Authors:
    • Raffaella Fazzina
    • Lorenza Lombardini
    • Laura  Mezzanotte
    • Aldo  Roda
    • Patrizia Hrelia
    • Andrea Pession
    • Roberto  Tonelli
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Oncology and Hematology, Sant' Orsola Hospital, University of Bologna, Bologna, Italy, Department of Pediatric Oncology and Hematology, Sant' Orsola Hospital, University of Bologna, Bologna, Italy, Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy, Department of Pharmacology, University of Bologna, Bologna, Italy
  • Pages: 621-628
    |
    Published online on: May 31, 2012
       https://doi.org/10.3892/ijo.2012.1504
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Abstract

Chromosomal translocations involving the MLL gene on 11q23 present frequent abnormalities in pediatric, adult and therapy-related acute leukemias, and are generally associated with aggressive disease and poor prognosis. Here, we report bioluminescent acute leukemia xenograft mouse models of the most frequent and aggressive MLL-related acute leukemias (infant and adult MLL-AF9, MLL-ENL, MLL-AF4). Four acute leukemia cell lines carrying MLL-related translocations were stably transduced with a firefly luciferase transgene and injected intravenously into NOD/SCID mice. Leukemia progression was monitored by in vivo bioluminescence imaging (BLI). All mice developed MLL-related acute leukemia. The four MLL-related acute leukemia models showed a different course of infant and adult MLL-AF9 acute myeloid leukemia, and a rapid aggressiveness of MLL-ENL acute lymphoblastic leukemia and MLL-AF4 acute biphenotypic leukemia. Tissue analysis and RT-PCR of bone marrow, spleen and liver from the mice confirmed the BL results. To validate BLI for the detection of a therapeutic response, systemic treatment with an anti-luciferase-targeting siRNA (siLuc) complexed with cationic nanoparticles was administered to mice with MLL-AF4 acute lymphoblastic leukemia. The BLI signal showed a reduction following treatment with siLuc compared to the control mice. These mouse models present MLL-related acute leukemia evolution similar to the human counterparts. Moreover, they are non-invasive, rapid and sensitive models, suitable for the in vivo study of MLL-related acute leukemias. Finally, BLI showed in vivo luminescence downmodulation obtained by systemic treatment with luciferase-targeting siRNA nanoparticle complexes, confirming that these MLL-related leukemia mouse models are optimal for the evaluation and selection of delivery systems for siRNA and other new biotechnological pharmaceuticals.
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Copy and paste a formatted citation
Spandidos Publications style
Fazzina R, Lombardini L, Mezzanotte L, Roda A, Hrelia P, Pession A and Tonelli R: Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles. Int J Oncol 41: 621-628, 2012.
APA
Fazzina, R., Lombardini, L., Mezzanotte, L., Roda, A., Hrelia, P., Pession, A., & Tonelli, R. (2012). Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles. International Journal of Oncology, 41, 621-628. https://doi.org/10.3892/ijo.2012.1504
MLA
Fazzina, R., Lombardini, L., Mezzanotte, L., Roda, A., Hrelia, P., Pession, A., Tonelli, R."Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles". International Journal of Oncology 41.2 (2012): 621-628.
Chicago
Fazzina, R., Lombardini, L., Mezzanotte, L., Roda, A., Hrelia, P., Pession, A., Tonelli, R."Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles". International Journal of Oncology 41, no. 2 (2012): 621-628. https://doi.org/10.3892/ijo.2012.1504
Copy and paste a formatted citation
x
Spandidos Publications style
Fazzina R, Lombardini L, Mezzanotte L, Roda A, Hrelia P, Pession A and Tonelli R: Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles. Int J Oncol 41: 621-628, 2012.
APA
Fazzina, R., Lombardini, L., Mezzanotte, L., Roda, A., Hrelia, P., Pession, A., & Tonelli, R. (2012). Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles. International Journal of Oncology, 41, 621-628. https://doi.org/10.3892/ijo.2012.1504
MLA
Fazzina, R., Lombardini, L., Mezzanotte, L., Roda, A., Hrelia, P., Pession, A., Tonelli, R."Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles". International Journal of Oncology 41.2 (2012): 621-628.
Chicago
Fazzina, R., Lombardini, L., Mezzanotte, L., Roda, A., Hrelia, P., Pession, A., Tonelli, R."Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles". International Journal of Oncology 41, no. 2 (2012): 621-628. https://doi.org/10.3892/ijo.2012.1504
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