MEF2C-dysregulated pediatric T-cell acute lymphoblastic leukemia is associated with CDKN1B deletions and a poor response to glucocorticoid therapy.

Details

Serval ID
serval:BIB_9A943E62FE54
Type
Article: article from journal or magazin.
Collection
Publications
Title
MEF2C-dysregulated pediatric T-cell acute lymphoblastic leukemia is associated with CDKN1B deletions and a poor response to glucocorticoid therapy.
Journal
Leukemia & lymphoma
Author(s)
Colomer-Lahiguera S., Pisecker M., König M., Nebral K., Pickl W.F., Kauer M.O., Haas O.A., Ullmann R., Attarbaschi A., Dworzak M.N., Strehl S.
ISSN
1029-2403 (Electronic)
ISSN-L
1026-8022
Publication state
Published
Issued date
12/2017
Peer-reviewed
Oui
Volume
58
Number
12
Pages
2895-2904
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease in which multiple genetic abnormalities cooperate in the malignant transformation of T-lymphoid progenitors. Although in pediatric T-ALL, CDKN1B deletions occur in about 12% of the cases and represent one of the most frequent copy number alterations, neither their association with other genetic alterations nor the clinical characteristics of these patients have been determined yet. In this study, we show that loss of CDKN1B increased the prevalence of cell cycle regulator defects in immature T-ALL, usually only ascribed to CDKN2A/B deletions, and that CDKN1B deletions frequently coincide with expression of MEF2C, considered as one of the driving oncogenes in immature early T-cell precursor (ETP) ALL. However, MEF2C-dysregulation was only partially associated with the immunophenotypic characteristics used to define ETP-ALL. Furthermore, MEF2C expression levels were significantly associated with or may even be predictive of the response to glucocorticoid treatment.
Keywords
Adolescent, Biomarkers, Cell Line, Child, Child, Preschool, Cluster Analysis, Cyclin-Dependent Kinase Inhibitor p27/genetics, Cyclin-Dependent Kinase Inhibitor p27/metabolism, DNA Copy Number Variations, Female, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Glucocorticoids/therapeutic use, Humans, Immunophenotyping, Infant, MEF2 Transcription Factors/genetics, MEF2 Transcription Factors/metabolism, Male, Pharmacogenomic Variants, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics, Treatment Outcome, CDKN1B deletion, MEF2C dysregulation, T-cell acute lymphoblastic leukemia, glucocorticoid response, immunophenotype
Pubmed
Web of science
Create date
10/02/2021 19:20
Last modification date
12/04/2021 14:27
Usage data