1, 25-OH2 vitamin D3 and AKT-inhibition increase glucocorticoid induced apoptosis in a model of T-cell acute lymphoblastic leukemia (ALL). (2018)

• Record Type: Journal Article
• Authors: Pistor, Maximilian; Schrewe, Lisa; Haupeltshofer, Steffen; Miclea, Andrei; Faissner, Simon; Chan, Andrew; Hoepner, Robert
• Is Part Of: Leukemia research reports. Volume 9(2018)
• Page Start: 38
• Page End: 41
• Publication Date: 2018
• Subjects: Calcitriol -- MK-2206 -- Ruxolitinib -- Steroid resistance -- Jurkat; Leukemia -- Periodicals; Lymphomas -- Periodicals; Multiple myeloma -- Periodicals; Leukemia -- Periodicals; Lymphoma -- Periodicals; Multiple Myeloma -- Periodicals; Hematologic Neoplasms -- Periodicals; Leukemia; Lymphomas; Multiple myeloma; Electronic journals; Periodicals; 616.9941905
• DOI: 10.1016/j.lrr.2018.01.003
• Languages: English
• ISSNs: 2213-0489

Abstract

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.