Molecular characterization of the response to conventional chemotherapeutics in Pro-B-ALL cell lines in terms of tumor relapse

Little is known about optimally applying chemotherapeutic agents in a specific temporal sequence to rapidly reduce the tumor load and to improve therapeutic efficacy. The clinical optimization of drug efficacy while reducing side effects is still restricted due to an incomplete understanding of the...

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Main Authors: Gladbach, Yvonne S. (Author) , Kohrt, Lisa-Madeleine (Author) , Roolf, Catrin (Author) , Beck, Julia (Author) , Schütz, Ekkehard (Author) , Fuellen, Georg (Author) , Junghanß, Christian (Author) , Murua Escobar, Hugo Istvan (Author) , Hamed, Mohamed (Author)
Format: Article (Journal)
Language:English
Published: 14 July 2022
In: Genes
Year: 2022, Volume: 13, Issue: 7, Pages: 1-16
ISSN:2073-4425
DOI:10.3390/genes13071240
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/genes13071240
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2073-4425/13/7/1240
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Author Notes:Yvonne Saara Gladbach, Lisa-Madeleine Sklarz, Catrin Roolf, Julia Beck, Ekkehard Schütz, Georg Fuellen, Christian Junghanss, Hugo Murua Escobar and Mohamed Hamed
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Summary:Little is known about optimally applying chemotherapeutic agents in a specific temporal sequence to rapidly reduce the tumor load and to improve therapeutic efficacy. The clinical optimization of drug efficacy while reducing side effects is still restricted due to an incomplete understanding of the mode of action and related tumor relapse mechanisms on the molecular level. The molecular characterization of transcriptomic drug signatures can help to identify the affected pathways, downstream regulated genes and regulatory interactions related to tumor relapse in response to drug application. We tried to outline the dynamic regulatory reprogramming leading to tumor relapse in relapsed MLL-rearranged pro-B-cell acute lymphoblastic leukemia (B-ALL) cells in response to two first-line treatments: dexamethasone (Dexa) and cytarabine (AraC). We performed an integrative molecular analysis of whole transcriptome profiles of each treatment, specifically considering public knowledge of miRNA regulation via a network-based approach to unravel key driver genes and miRNAs that may control the relapse mechanisms accompanying each treatment. Our results gave hints to the crucial regulatory roles of genes leading to Dexa-resistance and related miRNAs linked to chemosensitivity. These genes and miRNAs should be further investigated in preclinical models to obtain more hints about relapse processes.
Item Description:Gesehen am 19.08.2022
Physical Description:Online Resource
ISSN:2073-4425
DOI:10.3390/genes13071240