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2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner
Joint Authors
Leni, Zaira
Arcaro, Alexandre
Ćwiek, Paulina
Dimitrova, Valeriya
Dulcey, Andrea S.
Zamboni, Nicola
Simillion, Cedric
Rossi, Geetha
Leibundgut, Kurt
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-07-26
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents.
Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome.
We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells.
Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner.
Unlike solid tumors, where 2-deoxy-D-glucose promotes inhibition of glycolysis by hexokinase II exclusively under hypoxic conditions, we were able to show that the antileukemic effects of 2-deoxy-D-glucose are far more complex in leukemia.
We demonstrate a hexokinase II-independent cell viability decrease and apoptosis induction of the glucose analog in leukemia.
Additionally, due to the structural similarity of 2-deoxy-D-glucose with mannose, we could confirm that the mechanism by which 2-deoxy-D-glucose predominantly acts in leukemia is via modification in N-linked glycosylation, leading to endoplasmic reticulum stress and consequently induction of the unfolded protein response.
American Psychological Association (APA)
Leni, Zaira& Ćwiek, Paulina& Dimitrova, Valeriya& Dulcey, Andrea S.& Zamboni, Nicola& Simillion, Cedric…[et al.]. 2017. 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1194079
Modern Language Association (MLA)
Leni, Zaira…[et al.]. 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-15.
https://search.emarefa.net/detail/BIM-1194079
American Medical Association (AMA)
Leni, Zaira& Ćwiek, Paulina& Dimitrova, Valeriya& Dulcey, Andrea S.& Zamboni, Nicola& Simillion, Cedric…[et al.]. 2-Deoxy-D-glucose Restore Glucocorticoid Sensitivity in Acute Lymphoblastic Leukemia via Modification of N-Linked Glycosylation in an Oxygen Tension-Independent Manner. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1194079
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1194079