دورية أكاديمية
أعرض في EDS

Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia.

التفاصيل البيبلوغرافية
العنوان: Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia.
المؤلفون: Mochmann LH; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Treue D; Institute of Pathology Berlin, Charité - Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany., Bockmayr M; Institute of Pathology Berlin, Charité - Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany.; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Silva P; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Zasada C; Berlin Institute for Medical Systems Biology (BIMSB) at Max Delbruck Center for Molecular Medicine, Berlin, Germany., Mastrobuoni G; Berlin Institute for Medical Systems Biology (BIMSB) at Max Delbruck Center for Molecular Medicine, Berlin, Germany., Bayram S; Berlin Institute for Medical Systems Biology (BIMSB) at Max Delbruck Center for Molecular Medicine, Berlin, Germany., Forbes M; Berlin Institute for Medical Systems Biology (BIMSB) at Max Delbruck Center for Molecular Medicine, Berlin, Germany., Jurmeister P; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany., Liebig S; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Blau O; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Schleich K; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany., Splettstoesser B; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Bavaria, Germany., Nordmann TM; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Bavaria, Germany., von der Heide EK; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Isaakidis K; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Schulze V; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Busch C; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Siddiq H; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Schlee C; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, a Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany., Hester S; Department of Biochemistry, Oxford University, Oxford, UK., Fransecky L; Department of Hematology and Oncology, UKSH, Campus Kiel, Kiel, Germany., Neumann M; Department of Hematology and Oncology, UKSH, Campus Kiel, Kiel, Germany., Kempa S; Berlin Institute for Medical Systems Biology (BIMSB) at Max Delbruck Center for Molecular Medicine, Berlin, Germany. Stefan.Kempa@mdc-berlin.de., Klauschen F; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany. Frederick.Klauschen@med.uni-muenchen.de.; Institute of Pathology Berlin, Charité - Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany. Frederick.Klauschen@med.uni-muenchen.de.; German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany. Frederick.Klauschen@med.uni-muenchen.de., Baldus CD; Department of Hematology and Oncology, UKSH, Campus Kiel, Kiel, Germany. Claudia.Baldus@uksh.de.
المصدر: Cancer gene therapy [Cancer Gene Ther] 2024 Sep; Vol. 31 (9), pp. 1344-1356. Date of Electronic Publication: 2024 Jun 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9432230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5500 (Electronic) Linking ISSN: 09291903 NLM ISO Abbreviation: Cancer Gene Ther Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002->: London : Nature Publishing Group
Original Publication: Norwalk, CT : Appleton & Lange, c1994-
مواضيع طبية MeSH: Leukemia, Myeloid, Acute*/metabolism , Leukemia, Myeloid, Acute*/genetics , Leukemia, Myeloid, Acute*/drug therapy , Leukemia, Myeloid, Acute*/pathology , Proteomics*/methods, Humans ; Acetate-CoA Ligase/metabolism ; Acetate-CoA Ligase/genetics ; Cell Line, Tumor ; Cell Proliferation
مستخلص: Acute myeloid leukemia (AML) is a heterogeneous disease characterized by genomic aberrations in oncogenes, cytogenetic abnormalities, and an aberrant epigenetic landscape. Nearly 50% of AML cases will relapse with current treatment. A major source of therapy resistance is the interaction of mesenchymal stroma with leukemic cells resulting in therapeutic protection. We aimed to determine pro-survival/anti-apoptotic protein networks involved in the stroma protection of leukemic cells. Proteomic profiling of cultured primary AML (n = 14) with Hs5 stroma cell line uncovered an up-regulation of energy-favorable metabolic proteins. Next, we modulated stroma-induced drug resistance with an epigenetic drug library, resulting in reduced apoptosis with histone deacetylase inhibitor (HDACi) treatment versus other epigenetic modifying compounds. Quantitative phosphoproteomic probing of this effect further revealed a metabolic-enriched phosphoproteome including significant up-regulation of acetyl-coenzyme A synthetase (ACSS2, S30) in leukemia-stroma HDACi treated cocultures compared with untreated monocultures. Validating these findings, we show ACSS2 substrate, acetate, promotes leukemic proliferation, ACSS2 knockout in leukemia cells inhibits leukemic proliferation and ACSS2 knockout in the stroma impairs leukemic metabolic fitness. Finally, we identify ACSS1/ACSS2-high expression AML subtype correlating with poor overall survival. Collectively, this study uncovers the leukemia-stroma phosphoproteome emphasizing a role for ACSS2 in mediating AML growth and drug resistance.
(© 2024. The Author(s).)
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المشرفين على المادة: EC 6.2.1.1 (Acetate-CoA Ligase)
EC 6.2.1.1 (ACSS2 protein, human)
تواريخ الأحداث: Date Created: 20240608 Date Completed: 20240916 Latest Revision: 20240924
رمز التحديث: 20240925
مُعرف محوري في PubMed: PMC11405269
DOI: 10.1038/s41417-024-00785-5
PMID: 38851813
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5500
DOI:10.1038/s41417-024-00785-5