Journal article

Antagonism between MCL-1 and PUMA governs stem/progenitor cell survival during hematopoietic recovery from stress

Alex RD Delbridge, Joseph T Opferman, Stephanie Grabow, Andreas Strasser

Blood | AMER SOC HEMATOLOGY | Published : 2015

Abstract

Understanding the critical factors that govern recovery of the hematopoietic system from stress, such as during anticancer therapy and bone marrow transplantation, is of clinical significance. We investigated the importance of the prosurvival proteins myeloid cell leukemia-1 (MCL-1) and B-cell lymphoma-extra large (BCL-XL) in stem/progenitor cell survival and fitness during hematopoietic recovery from stress. Loss of a single Mcl-1 allele, which reduced MCL-1 protein levels, severely compromised hematopoietic recovery from myeloablative challenge and following bone marrow transplantation, whereas BCL-XL was dispensable in both contexts. We identified inhibition of proapoptotic p53 upregulate..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by NHMRC Senior Principal Research Fellow [SPRF] Fellowship


Awarded by Leukemia & Lymphoma Society (Specialized Center of Research [SCOR])


Awarded by National Institutes of Health National Heart, Lung, and Blood Institute


Awarded by Cancer Center Support Grant


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Funding Acknowledgements

This work was supported by grants and fellowships from the Cancer Council of Victoria (S.G. and A.R.D.D., Sydney Parker Smith Postdoctoral Research Fellowship), Lady Tata Postdoctoral Fellowship (S.G.), the National Health and Medical Research Council (NHMRC; program grant no. 1016701, NHMRC Senior Principal Research Fellow [SPRF] Fellowship 1020363 [A. S.]), and the Leukemia & Lymphoma Society (Specialized Center of Research [SCOR] grant no. 7001-13), Melbourne International Research Scholarship (University of Melbourne [S.G.]), Melbourne International Fee Remission Scholarship (University of Melbourne [S.G.]), Australian Postgraduate Award (A.R.D.D.) and Cancer Therapeutics Cooperative Research Centre (CRC) Top-up Scholarship (S.G. and A.R.D.D.), National Institutes of Health National Heart, Lung, and Blood Institute (R01HL102175, J.T.O.), American Lebanese Syrian Associate Charities (ALSAC; J.T.O.), and a Cancer Center Support Grant P30CA021765 (J.T.O.). This work was made possible by operational infrastructure grants through the Australian Government Independent Medical Research Institutes Infrastructure Support Scheme (IRIISS) and the Victorian State Government Operational Infrastructure Support (OIS).