Early and Very Early GRIM19 and MCL1 Expression Are Correlated to Late Acquired Prednisolone Effects in a T-Cell Acute Leukemia Cell Line.


Journal

Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103

Informations de publication

Date de publication:
2021
Historique:
entrez: 13 1 2022
pubmed: 14 1 2022
medline: 15 1 2022
Statut: ppublish

Résumé

Glucocorticoids (GCs) are still first-line drugs for the treatment of childhood acute lymphoblastic leukemia (ALL). Prednisolone is a corticosteroid and one of the most important agents in the treatment of ALL. We report here a study of Prednisolone treatment using as a model a leukemia cell line with subsequent investigation of resistance-related gene expression. Gene silencing has been used in order to identify significant targets of resistance to GC-induced apoptosis in ALL cells. We analyzed effects of increasing doses of Prednisolone on ALL cell survival and growth, and we monitored immediate effects on gene expression through gene expression assays. We determined Prednisolone cytotoxicity and cell cycle distribution as well as DNA content. Upon treatment with escalating Prednisolone concentration, we observed a gradual decline in cell survival. MCL1 and GRIM19 were investigated as possible genes for the intrinsic capacity of this cell line to respond to corticosteroid and a snapshot of early changes was examined. Early MCL1 and GRIM19 expression correlated significantly to late GC-induced apoptosis. Prednisolone competitively induces MCL1 expression. Consistently with previous studies on primary leukemia blasts, cells are sensitive to proteasome inhibitor MG132; no interference of Prednisolone with MG132 effects on this cell line was noted. The inherent plasticity of clinically evolving cancer justifies approaches to characterize and prevent undesirable activation of early oncogenic pathways. Study of the pattern of intracellular signal pathway activation by anticancer drugs can lead to development of efficient treatment strategies by reducing detrimental secondary effects.

Identifiants

pubmed: 35023102
doi: 10.1007/978-3-030-78787-5_20
doi:

Substances chimiques

MCL1 protein, human 0
Myeloid Cell Leukemia Sequence 1 Protein 0
Prednisolone 9PHQ9Y1OLM

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

147-160

Informations de copyright

© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.

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Auteurs

Lambrou G (L)

National and Kapodistrian University of Athens, First Department of Pediatrics, Choremeio Research Laboratory, Athens, Greece. glamprou@med.uoa.gr.

Maria Adamaki (M)

National and Kapodistrian University of Athens, First Department of Pediatrics, Choremeio Research Laboratory, Athens, Greece.

Kyriaki Hatziagapiou (K)

National and Kapodistrian University of Athens, First Department of Pediatrics, Choremeio Research Laboratory, Athens, Greece.

Styliani A Geronikolou (SA)

Biomedical Research Foundation of Academy of Athens, Clinical, Translational, Experimental Surgery Research Centerment of Pediatrics, Athens, Greece.

Athanasios N Tsartsalis (AN)

Naval Hospital of Athens, Department of Endocrinology Diabetes and Metabolism, Athens, Greece.

Spiros Vlahopoulos (S)

National and Kapodistrian University of Athens, First Department of Pediatrics, Choremeio Research Laboratory, Athens, Greece.

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