Journal article
Loss of a Single Mcl-1 Allele Inhibits MYC-Driven Lymphomagenesis by Sensitizing Pro-B Cells to Apoptosis
S Grabow, ARD Delbridge, BJ Aubrey, CJ Vandenberg, A Strasser
Cell Reports | Published : 2016
Abstract
MCL-1 is critical for progenitor cell survival during emergency hematopoiesis, but its role in sustaining cells undergoing transformation and in lymphomagenesis is only poorly understood. We investigated the importance of MCL-1 in the survival of B lymphoid progenitors undergoing MYC-driven transformation and its functional interactions with pro-apoptotic BIM and PUMA and the tumor suppressor p53 in lymphoma development. Loss of one Mcl-1 allele almost abrogated MYC-driven-lymphoma development owing to a reduction in lymphoma initiating pre-B cells. Although loss of the p53 target PUMA had minor impact, loss of one p53 allele substantially accelerated lymphoma development when MCL-1 was limi..
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Awarded by Leukemia and Lymphoma Society
Funding Acknowledgements
We thank Dr. J.M. Adams for comments on the manuscript; Drs. P.M. Colman, G.L. Kelly, and L.A. O'Reilly for stimulating discussions and support; Drs. P. Bouillet, S. Cory, A. Villunger, and T. Jacks for mouse strains; Drs. S. Wilcox and A. Kueh for DNA sequence analysis; J. Mansheim, S. O'Connor, K. Walker, C. Gatt, S. Allan, T. Bertenis, C. D'Alessandro, and G. Siciliano for animal care; J. Corbin and J. McManus for automated blood analysis; B. Helbert for mouse genotyping; and E. Tsui, V. Babo, K. Weston, Y. Hoang, C. Tsui, and S. Hasanein for histology. Our research was supported by grants and fellowships from the Cancer Council of Victoria (postdoctoral fellowship to S.G. and A.R.D.D.), the Lady Tata Memorial Trust (postdoctoral research award to S.G.), Leukaemia Foundation Australia (postdoctoral fellowship to S.G.), the National Health and Medical Research Council (program grant 1016701; NHMRC fellowship 1020363, all to A. S.), the Leukemia and Lymphoma Society (SCOR grant 7001-03 to A. S.), the estate of Anthony (Toni) Redstone OAM, University of Melbourne International Research and International Fee Remission Scholarships (S.G.), Australian Postgraduate Award (A.R.D.D.), Leukaemia Foundation National Research Program Clinical PhD Scholarship (B.J.A.), Cancer Therapeutics CRC top-up scholarship (S.G. and A.R.D.D.), and the operational infrastructure grants through the Australian Government IRIISS and the Victorian State Government OIS. S.G., A.R.D.D., B.J.A., C.J.V., and A.S. are employed by the Walter and Eliza Hall Institute, which receives milestone payments from Genentech and AbbVie for the development of ABT-199 for anti-cancer therapy.