Poster Presentation 25th Lorne Cancer Conference 2013

Mcl-1 sustains survival of Myc over-expressing pre-leukaemic B lymphoid cells in Eμ-myc transgenic mice (#193)

Stephanie Grabow 1 2 3 , Alex RD Delbridge 1 2 3 , Gemma L Kelly 1 , Priscilla N Kelly 4 , Philippe Bouillet 1 , Andreas Strasser 1
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia
  2. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  3. Cancer Therapeutics CRC, Melbourne, Victoria, Australia
  4. Metabolism Branch, National Cancer Institute/NIH, Bethesda, Maryland, USA
Evasion of cell death is critical for tumorigenesis and it is widely believed that expression of pro-survival Bcl-2 family members is essential to sustain survival of cells undergoing neoplastic transformation. Previous studies have shown that Bcl-xL, is critical for Myc-induced pre-B/B lymphoma development. It remains, however, unclear whether Bcl-xL is the sole pro-survival Bcl-2 family member required for Myc-induced tumorigenesis. Mcl-1 is critical for cell survival during the early stages of B lymphopoiesis and is expressed at abnormally high levels in several types of human B cell lymphomas where it causes chemo-resistance. We therefore examined the role of Mcl-1 in lymphoma development in Eµ-myc transgenic mice, a model of human Burkitt’s lymphoma, in which Myc over-expression under control of the immunoglobulin heavy chain gene enhancer (Eµ) causes accumulation of pre-leukaemic pro-B/pre-B cells, which further progress to a malignant state. Remarkably, our results show that loss of only one allele of mcl-1 is sufficient to diminish the pre-leukaemic expansion of B lymphoid cells and to substantially prolong survival of Eµ-myc transgenic mice.