Journal article
Hierarchy for targeting prosurvival BCL2 family proteins in multiple myeloma: Pivotal role of MCL1
JN Gong, T Khong, D Segal, Y Yao, CD Riffkin, JM Garnier, S Lin Khaw, G Lessene, A Spencer, MJ Herold, AW Roberts, DCS Huang
Blood | Published : 2016
Abstract
New therapeutic targets are needed to address the poor prognosis of patients with highrisk multiple myeloma. Myeloma cells usually express a range of the prosurvival BCL2 proteins. To define the hierarchy of their relative importance for maintaining the survival of myeloma cells, we targeted each of them in a large panel of cell lines, using pharmacological inhibitors or gene editing or by peptide-based approaches, alone or in combination. The majority of well-established immortalized cell lines (17/25) or lowpassage myeloma cell lines (5/7) are readily killed when MCL1 is targeted, even including those cell lines sensitive to BCL2 inhibition. Targeting MCL1 also constrained the growth of my..
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Awarded by Leukemia and Lymphoma Society
Funding Acknowledgements
This work is supported by scholarships, fellowships, and grants from the Australian National Health and Medical Research Council (research fellowships to A.W.R. and D.C.S.H.; project grant 1057742 [D.C.S.H.]; program grants 1016647 and 1016701; and Independent Research Institutes Infrastructure Support Scheme [grant 9000220]), the Cancer Council Victoria (grant-in-aid to A.W.R. and D.C.S.H.), the Leukemia and Lymphoma Society (Specialized Centers of Research grants 7001-13), the Australian Cancer Research Foundation, a Victorian State Government Operational Infrastructure Support grant, and the China Scholarship Council (award to Y.Y.). A.W.R. holds the Metcalf Chair of Leukaemia Research at the University of Melbourne.