Introduction:
Class I HDACi has been shown to be effective for t(4;11) fusion proteins, as it abolishes
functions from MLL-AF4 (to set a leukemic expression profile) while wildtype MLL becomes
activated. In addition, functions deriving from AF4-MLL (to set active chromatin)
can be counteracted by a dnTapsase1 mutant (dnTASP1), which in turn causes the degradation
of the AF4-MLL fusion protein. Here we evaluated the combination of both treament
options on viability and apoptosis of t(4,11) cells.
Methods:
IC50 values were elucidated for three cass I HDACi drugs and used for a specific treatment
schedule that allows to measure viability and apoptosis in transgenic SEM cells, expressing
dnTASP1 in a Doxycyclin-inducible fashion.
Results & Conclusion:
Class I HDACi are potent inhibitors that can be still enhanced by the expression of
dnTASP1. Data of this optimized protocol in conjunction with standard chemotherapeutics
on the survival will be presented.
