Journal article
Inhibition of Pol I transcription treats murine and human AML by targeting the leukemia-initiating cell population
N Hein, DP Cameron, KM Hannan, NYN Nguyen, CY Fong, J Sornkom, M Wall, M Pavy, C Cullinane, J Diesch, JR Devlin, AJ George, E Sanij, J Quin, G Poortinga, I Verbrugge, A Baker, D Drygin, SJ Harrison, JD Rozario Show all
Blood | AMER SOC HEMATOLOGY | Published : 2017
Abstract
Despite the development of novel drugs, the prospects for many patients with acute myeloid leukemia (AML) remain dismal. This study reveals that the selective inhibitor of RNA polymerase I (Pol I) transcription, CX-5461, effectively treats aggressive AML, including mixed-lineage leukemia-driven AML, and outperforms standard chemotherapies. In addition to the previously characterized mechanism of action of CX-5461 (ie, the induction of p53-dependent apoptotic cell death), the inhibition of Pol I transcription also demonstrates potent efficacy in p53null AML in vivo. This significant survival advantage in both p53WT and p53null leukemic mice treated with CX-5461 is associated with activation o..
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Grants
Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by NHMRC program
Awarded by Cancer Council of Victoria
Funding Acknowledgements
This work was supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (#1043884, 251608, 566702, 166908, 251688, 509087, 400116, 400120, and 566876) and an NHMRC program grant (#1053792), and the Cancer Council of Victoria grant-in-aid (#1084545). The researchers were funded by the following: NHMRC fellowships (R.D.H., R.B.P., R.W.J., and G.A.M.), Cancer Council of Victoria, Cancer Council of Australian Capital Territory, Sir Edward Weary Dunlop fellowship (G.A.M.), and the Leukemia Foundation of Australia (grant-in-aid to M.W., and Ph.D. scholarships to D.P.C. and J.D.).