GRU Cancer Center researchers have identified a potential treatment strategy for a rare but aggressive, largely incurable type of leukemia/lymphoma that is resistant to all current therapies. By developing mouse models of the disease, the Cowell laboratory was able to track important changes in gene expression related to disease progression. These changes indicated that multiple cancer-inducing signaling pathways were activated in the disease. Simultaneous targeting of these pathways was found to inhibit tumor cell growth, suggesting that this multi-pronged treatment strategy may break through the current stalemate in treatment options.
The disease under scrutiny in this study is blood cancer that results from chromosomal aberrations related to the FGFR1 gene. Subsequent abnormal fusion of two proteins leads to acute myeloid leukemia (AML), often with lymphomas. Previously reported disease models have mimicked the human disease, but not to the point of progressing to AML. Two novel mouse models of the disease developed and presented here by the Cowell laboratory rectify this shortcoming. Specifically, their model using human cord blood-derived blood stem cells (marked by the CD34+ protein) recapitulates the human disease – including progression to AML – in immunocompromised mice. These results provide the first opportunity to study the molecular events leading from blood stem cells to AML and have therefore permitted advanced study into defining new therapeutic strategies for testing in preclinical trials.[Ren M, Qin H, Kitamura E, and Cowell JC. Disregulated signaling pathways in the development of CNTRL-FGFR1-induced myeloid and lymphoid malignancies associated with FGFR1 in human and mouse models. Blood 2013 Aug 8;122(6):1007-16