Journal article
ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells
LCY Chee, J Hendy, LE Purton, GA McArthur
Leukemia | Published : 2013
DOI: 10.1038/leu.2012.362
Abstract
All-trans retinoic acid (ATRA) is used successfully in the treatment of acute promyelocytic leukemia (APL). ATRA enhances hematopoietic stem cell self-renewal through retinoic acid receptor (RAR)γ activation while promoting differentiation of committed myeloid progenitors through RARα activation. Its lack of success in the treatment of non-APL acute myeloid leukemia (AML) may be related to ATRA's non-selectivity for the RARα and RARγ isotypes, and specific RARα activation may be more beneficial in promoting myeloid differentiation. To investigate this hypothesis, the effects of ATRA and the specific RARα agonist NRX195183 was assessed in AML1-ETO (AE)-expressing murine bone marrow (BM) proge..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported in part by grants from the National Health and Medical Research Council (NHMRC, Canberra, Australia) Project Grant 350272 (GAM and LEP), NHMRC Practitioner Fellowship (GAM) and CSL Limited (Victoria, Australia) (LCYC). LCYC is also a recipient of a University of Melbourne Faculty of Medicine, Dentistry and Health Sciences Research Scholarship and a Royal Australasian College of Physicians Arnott Research Entry Scholarship for Cancer Research. LEP is an NHMRC Senior Research Fellow. GAM was a recipient of a Cancer Council of Victoria Sir Edward Weary Dunlop Clinical Research Fellowship. Many thanks to Prof. James R Downing (St. Jude Children's Research Hospital, Memphis, TN, USA) for provision of the AML1-ETO-stop/+ mice, Dr David Curtis (Rotary Bone Marrow Research Laboratories, The Royal Melbourne Hospital, Melbourne, Victoria, Australia) for provision of the Mx1-Cre<SUP>+</SUP> mice, Dr David Izon (St. Vincent's Institute, Fitzroy, Victoria, Australia) for provision of the MigR1 vector, Dr Carleen Cullinane and the Translational Research Laboratory staff for technical assistance with mice procedures, Rebecca Driessen from the Microarray Core for processing of RNA samples, Jason Ellul from the Bioinformatics Department for assistance with analysis, Dr Rosh Chandraratna from IO Therapeutics for helpful discussions and the PMCC Animal Facility staff for care of experimental mice.