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Transcript 
Inhibition of Pol I transcription treats murine and human
AML by targeting the leukemia-initiating cell population
by Nadine Hein, Donald P. Cameron, Katherine M. Hannan, Nhu-Y N. Nguyen, Chun
Yew Fong, Jirawas Sornkom, Meaghan Wall, Megan Pavy, Carleen Cullinane,
Jeannine Diesch, Jennifer R. Devlin, Amee J. George, Elaine Sanij, Jaclyn Quin,
Gretchen Poortinga, Inge Verbrugge, Adele Baker, Denis Drygin, Simon J. Harrison,
James D. Rozario, Jason A. Powell, Stuart M. Pitson, Johannes Zuber, Ricky W.
Johnstone, Mark A. Dawson, Mark A. Guthridge, Andrew Wei, Grant A. McArthur,
Richard B. Pearson, and Ross D. Hannan
Blood
Volume 129(21):2882-2895
May 25, 2017
©2017 by American Society of Hematology
MLL-driven leukemias are sensitive to inhibition of hyperactivated Pol I transcription in vitro.
Nadine Hein et al. Blood 2017;129:2882-2895
©2017 by American Society of Hematology
CX-5461 therapy delays disease progression and significantly extends survival in leukemic
mice.
Nadine Hein et al. Blood 2017;129:2882-2895
©2017 by American Society of Hematology
CX-5461 exhibits therapeutic potential in mouse and human AML independent of their p53
status.
Nadine Hein et al. Blood 2017;129:2882-2895
©2017 by American Society of Hematology
A single CX-5461 administration reduces the tumor burden in M/E leukemic mice.
Nadine Hein et al. Blood 2017;129:2882-2895
©2017 by American Society of Hematology
Pol I inhibition activates ATM/ATR-dependent signaling and alters cell-cycle progression in
human AML cell lines.
Nadine Hein et al. Blood 2017;129:2882-2895
©2017 by American Society of Hematology
Transcriptome analysis of M/E p53WT AML treated with CX-5461 by RNA sequencing revealed
induction of myeloid maturation.
Nadine Hein et al. Blood 2017;129:2882-2895
©2017 by American Society of Hematology
CX-5461 reduces the L-GMP and LIC population in MLL-driven AML. M/E p53WT or p53null AML
cells were engrafted into recipient C57Bl/6 mice and treated with CX-5461 for 48 or 72 hours
(p53WT 40 mg/kg, p53null 35 mg/kg).
Nadine Hein et al. Blood 2017;129:2882-2895
©2017 by American Society of Hematology
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