(Grembecka,
Nat. Chem. Biol. 2012; Dawson, Nature 2011;
Daigle, Cancer Cell 2011; Cao, Mol Cell 2014)
K79
K79
K79
K79
DOT1L
K4
K4
K4
Transcription aberrantly /
constantly ON
MLL
wt
HDACi???
(Stumpel DJ, Leukemia. 2012; Vilas-Zornoza
Leukemia. 2012; Bots, Blood 2014; Platzbecker,
Leukemia 2014; Stankov, Leukemia 2014)
HDACs??
pTEFb
PAFc
TIP60
Inhibition of DOT1L Methyltransferase activity
Inhibition of MLL methyltransferase activity
Inhibition of Menin-MLL interaction
Inhibition of BRD4
MLL
Minor groove
DNA binding
AT-hook
TRD
Break point
region
AF9
9 der(9) der(11) 11
MLL-AF9
t(9;11)(p22;q23)
