The NUP98-HOXD13 fusion oncogene induces thymocyte self-renewal via Lmo2/Lyl1
Benjamin J Shields, Christopher Slape, Ngoc Vo, Jacob T Jackson, Adriana Pliego-Zamora, Hansini Ranasinghe, Wei Shi, David J Curtis, Matthew P McCormack
Leukemia | NATURE PUBLISHING GROUP | Published : 2019
T cell acute lymphoblastic leukaemia (T-ALL) cases include subfamilies that overexpress the TAL1/LMO, TLX1/3 and HOXA transcription factor oncogenes. While it has been shown that TAL1/LMO transcription factors induce self-renewal of thymocytes, whether this is true for other transcription factor oncogenes is unknown. To address this, we have studied NUP98-HOXD13-transgenic (NHD13-Tg) mice, which overexpress HOXA transcription factors throughout haematopoiesis and develop both myelodysplastic syndrome (MDS) progressing to acute myeloid leukaemia (AML) as well as T-ALL. We find that thymocytes from preleukaemic NHD13-Tg mice can serially transplant, demonstrating that they have self-renewal ca..View full abstract
Awarded by Australian Government's National Health and Medical Research Council
The authors thank the Walter and Eliza Hall Institute (WEHI) Bioservices and Alfred Medical Research and Education Precinct (AMREP) animal services for mouse husbandry and the WEHI and AMREP Flow Cytometry Facilities. This work was supported by project grant (1031654 [to MPM, DJC] and 1104145 [to MPM]), a Senior Research Fellowship (to DJC) and the Independent Research Institute's Infrastructure Support Scheme from the Australian Government's National Health and Medical Research Council, grants-in-aid from the Cancer Council of Victoria (to MPM) and the Leukaemia Foundation of Australia (to MPM and CIS), a Future Fellowship from the Australian Research Council (to MPM) and a Victorian State Government Operational Infrastructure Support grant.