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The death-associated protein kinase 1 (DAPK1) : prognostic relevance in pediatric acute lymphoblastic leukemia (ALL) and evaluation as a therapeutic target

Ulrich, Sebastian Universität Ulm 2018

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  • Title:
    The death-associated protein kinase 1 (DAPK1) : prognostic relevance in pediatric acute lymphoblastic leukemia (ALL) and evaluation as a therapeutic target
  • Author: Ulrich, Sebastian
  • Universität Ulm
  • Subjects: Dapk1 ; Ddc 610 / Medicine & Health ; Leukemia; Genetics ; Death-Associated Protein Kinases ; Methylation ; Apoptosis ; Epigenomics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Leukämie ; Epigenetik ; Apoptosis ; Methylierung
  • Description: In the present study, we referred to previous published data that identified different engraftment phenotypes of patient-derived ALL-samples (Acute Lymphoblastic Leukemia) transplanted on NOD/SCID mice (Non Obese Diabetes/ Severe Combined Immunodeficiency), which demonstrated a connection between patient outcome and engraftment properties. A gene expression analysis of patient-derived xenograft samples identified altered expression levels of apoptosis-related genes, including the pro-apoptotic molecule DAPK1 (Death-Associated Protein Kinase 1) which was significantly downregulated in the TTLshort/ early relapse group (TTL = time to leukemia) compared to TTLlong on transcript level. As a first result of the present study we could confirm these findings and found reduced expression levels of DAPK1 protein in TTLshort compared with TTLlong in the same cohort as well. Out of a group of ten ALL-cell lines we identified two BCP-ALL (B-Cell Precursor-Acute Lymphoblastic Leukemia) (REH, NALM-6) and one mature B-ALL (TANOUE) as low expressing DAPK1 ALL cell lines and one T-ALL (JURKAT) that shows moderate expression levels of DAPK1. Treatment experiments with the DNMT-Inhibitor Decitabine were performed, showing a time- and dose-dependency of Decitabine-induced cell death in all four cell lines. Furthermore, we analyzed expression levels of DAPK1 upon Decitabine-treatment in all four cell lines. Upregulation of DAPK1 transcript expression...
  • Publisher: Universität Ulm
  • Creation Date: 2018
  • Language: English
  • Identifier: DOI: 10.18725/OPARU-5686
  • Source: DataCite

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