1. Academic Validation
  2. 1,25-OH2 vitamin D3 and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)

1,25-OH2 vitamin D3 and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)

  • Leuk Res Rep. 2018 Mar 17;9:38-41. doi: 10.1016/j.lrr.2018.01.003.
Maximilian Pistor 1 Lisa Schrewe 2 Steffen Haupeltshofer 1 Andrei Miclea 3 Simon Faissner 4 Andrew Chan 2 Robert Hoepner 2
Affiliations

Affiliations

  • 1 Department of Neurology, Neuroimmunology Lab, St. Josef Hospital, Ruhr University Bochum, Universitätsstrasse 150, 44801 Bochum, Germany.
  • 2 Department of Neurology, Inselspital, University Hospital Bern, Switzerland.
  • 3 Medical Faculty, Ruhr-University Bochum, Germany.
  • 4 Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Germany.
Abstract

In acute lymphoblastic leukemia (ALL), steroid resistance and hypovitaminosis D are both associated with a poor prognosis. We show that methylprednisolone, calcitriol and the AKT-inhibitor MK-2206 have a synergistic effect on the Apoptosis of steroid resistant T-ALL cells. Compared to methylprednisolone monotherapy, calcitriol increases methylprednisolone induced Apoptosis dose-dependently (1.37-1.92-fold; p < 0.05). Pre-incubation with calcitriol increases the apoptotic effect of MK-2206 even further (3.6-fold; p < 0.05). It also potentiates synergism between MK-2206 and methylprednisolone (vehicle control 38% vs. calcitriol 58%, p < 0.01). The combination of calcitriol and Akt inhibition should be investigated further as treatment options for steroid resistance in T-ALL.

Keywords

Calcitriol; Jurkat; MK-2206; Ruxolitinib; Steroid resistance.

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