Prophylactic treatment with the BH3 mimetic ABT-737 impedes Myc-driven lymphomagenesis in mice
PN Kelly, S Grabow, ARD Delbridge, JM Adams, A Strasser
Cell Death & Differentiation | NATURE PUBLISHING GROUP | Published : 2013
As many oncogenic changes, such as Myc overexpression, promote apoptosis, the survival of emerging neoplastic clones may often initially depend upon endogenous levels of particular pro-survival members of the Bcl-2 protein family. Pertinently, we recently showed that in lymphoma-prone Eμ-myc transgenic mice, which overexpress Myc in all B-lymphoid cells, endogenous Bcl-x(L) is critical for the survival, as well as the expansion of preneoplastic B-lymphoid cells and the development of malignant disease. This discovery raised the possibility that pharmacological blockade of Bcl-x(L) might impede Myc-driven lymphoma development. Indeed, we report here that treatment of preleukaemic Eμ-myc trans..View full abstract
Awarded by National Health and Medical Research Council (NHMRC Australia Fellowship)
Awarded by Leukemia and Lymphoma Society (SCOR Grant)
We thank Drs S Cory, D Huang and P Bouillet for providing mice, reagents and advice; M Cook, for preparing the ABT-737 for injections; K Vella, G Siciliano, D Cooper, N Iannarella, J Coughlin and Lisa Reid for animal care and help with ABT-737 treatment; J Corbin for automated blood analysis; B Helbert and C Young for genotyping; Dr. F Battye and his team for cell sorting, Dr. S Mihajlovic and his team for histological services and D Quilici, T Nikolaou and G Thomas for irradiation. This work was supported by grants and fellowships from the Cancer Council of Victoria (to PNK), the National Health and Medical Research Council (Program Grant No. 461221, NHMRC Australia Fellowship), the Leukemia and Lymphoma Society (SCOR Grant No. 7413) and operational infrastructure grants through the Australian Government IRISS and the Victorian State Government OIS. We acknowledge collaboration with Genentech and Abbott Laboratories on the development of BH3 mimetic drugs.