Can we develop relevant in vivo models of human leukemia using transplantation of these cells in the immunocompromised NOD/SCID or NOD/SCID/ beta2M mouse?
The model involves retroviral transduction of human HSC with AML1-ETO and a second, cooperating oncogene (that is identified in studies from Aim 1), and introduction of these cells into NOD/SCID mice. AML1-ETO expression is not sufficient by itself to induce leukemia in murine models, and our data confirms this in human HSC. We are interested in identifying cooperating signaling pathways that together with AML1-ETO will transform normal primary HSC into leukemic stem cells. With this knowledge, specific strategies for abrogating one or more of these signaling pathways can be applied to the treatment of the leukemia that is modeled in the NOD/SCID mice.
Wei, J., Wunderlich, M., Fox, C., Alvarez, S., Cigudosa, J.C., Wilhelm, J.E., Zheng, Y., Cancelas, J.A., Gu, Y., Jansen, M., DiMartino, J.F. and Mulloy, J.C. Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia. Cancer Cell. 2008 Jun;13(6):483-95.
Book Chapter
Wunderlich, M. and Mulloy, J.C. Model systems for examining effects of leukemia associated oncogenes in primary human CD34+ cells via retroviral transduction. In "Methods in Molecular Medicine-Childhood Leukaemia". Chi Wai Eric So, ed. Humana Press, in press.
Contact Us
For additional information, please contact
Dr. James Mulloy, Division of Experimental Hematology, at 513-636-1844. Dr. Mulloy's office can be found in room S7.603.
