1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)

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 methylpredniso...

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Autores principales: Pistor, Maximilian, Schrewe, Lisa, Haupeltshofer, Steffen, Miclea, Andrei, Faissner, Simon, Chan, Andrew, Hoepner, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993358/
https://www.ncbi.nlm.nih.gov/pubmed/29892547
http://dx.doi.org/10.1016/j.lrr.2018.01.003
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author Pistor, Maximilian
Schrewe, Lisa
Haupeltshofer, Steffen
Miclea, Andrei
Faissner, Simon
Chan, Andrew
Hoepner, Robert
author_facet Pistor, Maximilian
Schrewe, Lisa
Haupeltshofer, Steffen
Miclea, Andrei
Faissner, Simon
Chan, Andrew
Hoepner, Robert
author_sort Pistor, Maximilian
collection PubMed
description 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.
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spelling pubmed-59933582018-06-11 1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL) Pistor, Maximilian Schrewe, Lisa Haupeltshofer, Steffen Miclea, Andrei Faissner, Simon Chan, Andrew Hoepner, Robert Leuk Res Rep Article 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. Elsevier 2018-03-17 /pmc/articles/PMC5993358/ /pubmed/29892547 http://dx.doi.org/10.1016/j.lrr.2018.01.003 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Pistor, Maximilian
Schrewe, Lisa
Haupeltshofer, Steffen
Miclea, Andrei
Faissner, Simon
Chan, Andrew
Hoepner, Robert
1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)
title 1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)
title_full 1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)
title_fullStr 1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)
title_full_unstemmed 1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)
title_short 1,25-OH(2) vitamin D(3) and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)
title_sort 1,25-oh(2) vitamin d(3) and akt-inhibition increase glucocorticoid induced apoptosis in a model of t-cell acute lymphoblastic leukemia (all)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993358/
https://www.ncbi.nlm.nih.gov/pubmed/29892547
http://dx.doi.org/10.1016/j.lrr.2018.01.003
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