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

Maximilian Pistor; Lisa Schrewe; Steffen Haupeltshofer; Andrei Miclea; Simon Faissner; Andrew Chan; Robert Hoepner

doi:10.1016/j.lrr.2018.01.003

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

Maximilian Pistor, Lisa Schrewe, Steffen Haupeltshofer, Andrei Miclea, Simon Faissner, Andrew Chan, Robert Hoepner

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Pages (from-to)	38-41
Number of pages	4
Journal	Leukemia Research Reports
Volume	9
DOIs	https://doi.org/10.1016/j.lrr.2018.01.003
State	Published - 2018
Externally published	Yes

Keywords

Calcitriol
Jurkat
MK-2206
Ruxolitinib
Steroid resistance

Access to Document

10.1016/j.lrr.2018.01.003

Cite this

@article{95e6c3cca8b1481e8180c3bbf9f00da3,

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

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",

author = "Maximilian Pistor and Lisa Schrewe and Steffen Haupeltshofer and Andrei Miclea and Simon Faissner and Andrew Chan and Robert Hoepner",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

doi = "10.1016/j.lrr.2018.01.003",

language = "English",

volume = "9",

pages = "38--41",

journal = "Leukemia Research Reports",

issn = "2213-0489",

publisher = "Elsevier Ltd.",

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TY - JOUR

T1 - 1,25-OH2 vitamin D3 and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL)

AU - Pistor, Maximilian

AU - Schrewe, Lisa

AU - Haupeltshofer, Steffen

AU - Miclea, Andrei

AU - Faissner, Simon

AU - Chan, Andrew

AU - Hoepner, Robert

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Calcitriol

KW - Jurkat

KW - MK-2206

KW - Ruxolitinib

KW - Steroid resistance

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U2 - 10.1016/j.lrr.2018.01.003

DO - 10.1016/j.lrr.2018.01.003

M3 - Article

AN - SCOPUS:85056381011

SN - 2213-0489

VL - 9

SP - 38

EP - 41

JO - Leukemia Research Reports

JF - Leukemia Research Reports

ER -