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DOI: 10.1055/s-0039-1687133
Investigating HDACi and dnTaspase1 for the treatment of t(4;11) leukemic cells
Publication History
Publication Date:
20 May 2019 (online)
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.