Journal article
PUMA promotes apoptosis of hematopoietic progenitors driving leukemic progression in a mouse model of myelodysplasia
AA Guirguis, CI Slape, LM Failla, J Saw, CS Tremblay, DR Powell, F Rossello, A Wei, A Strasser, DJ Curtis
Cell Death and Differentiation | Published : 2016
DOI: 10.1038/cdd.2015.159
Abstract
Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis with resultant cytopenias. Increased apoptosis and aberrantly functioning progenitors are thought to contribute to this phenotype. As is the case for other malignancies, overcoming apoptosis is believed to be important in progression toward acute myeloid leukemia (AML). Using the NUP98-HOXD13 (NHD13) transgenic mouse model of MDS, we previously reported that overexpression of the anti-apoptotic protein BCL2, blocked apoptosis and improved cytopenias, paradoxically, delaying leukemic progression. To further understand this surprising result, we examined the role of p53 and its pro-apoptotic effectors, PUMA and NOXA i..
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Awarded by Cancer Council Victoria
Funding Acknowledgements
We thank Dr J Adams for providing mouse strains; S Beeraka for technical assistance; N Borg and K Spark for animal husbandry and the AMREP Flow Cytometry Core facility for its assistance with flow analysis and cell sorting. This study was supported by project grants from the Australian National Health and Medical Research Council (NHMRC) (628367) and Cancer Council Victoria awarded to CIS and DJC; a Viertel Senior Medical Research Fellowship awarded to DJC; a Leukaemia Foundation Clinical PhD Scholarship awarded to AAG; project grants from the NHMRC (1016701), Leukemia and Lymphoma society (700113), Cancer Council Victoria, an NHMRC SPRF fellowship (1020363) and the estate of Anthony (Toni) Redstone OAM awarded to AS.