Klin Padiatr 2019; 231(03): 160
DOI: 10.1055/s-0039-1687133
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Investigating HDACi and dnTaspase1 for the treatment of t(4;11) leukemic cells

A Wilhelm
1   Institute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany
,
R Marschalek
1   Institute of Pharmaceutical Biology/DCAL, Goethe-University of Frankfurt, Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
20 May 2019 (online)

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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.