Research Paper Volume 12, Issue 17 pp 16759—16774

HDAC4 inhibition disrupts TET2 function in high-risk MDS and AML

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Figure 6. TET2 agonist in combination with HDACi promotes potent anti-leukemia effects in vivo. (A) Schematic showing experimental protocol. 2.5 x 106 luciferase-expressing MDS-L cells were transplanted into NSGS recipient mice intravenously. Seven days later, baseline engraftment was detected by bioluminescence imaging. Drug treatment began on D7 via I.P. injection. MDS-L engraftment was detected at D21. (B) Pseudocolored bioluminescence images of NSGS mice transplanted with MDS-L cells and subjected to indicated drug treatment. Radiance is in units of “photons/second/cm2/steradian”. One mouse in the SAHA group died during drug administration (indicated by red X). (C) Total flux (photons/sec) of NSGS mice transplanted with MDS-L cells after indicated treatments. Signal intensity was quantified from each animal shown in panel b. (D) 5hmC levels (as quantified by flow cytometry) in peripheral blood cells of mice after indicated treatments.