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The proteogenomic subtypes of acute myeloid leukemia.
Jayavelu, Ashok Kumar; Wolf, Sebastian; Buettner, Florian; Alexe, Gabriela; Häupl, Björn; Comoglio, Federico; Schneider, Constanze; Doebele, Carmen; Fuhrmann, Dominik C; Wagner, Sebastian; Donato, Elisa; Andresen, Carolin; Wilke, Anne C; Zindel, Alena; Jahn, Dominique; Splettstoesser, Bianca; Plessmann, Uwe; Münch, Silvia; Abou-El-Ardat, Khali; Makowka, Philipp; Acker, Fabian; Enssle, Julius C; Cremer, Anjali; Schnütgen, Frank; Kurrle, Nina; Chapuy, Björn; Löber, Jens; Hartmann, Sylvia; Wild, Peter J; Wittig, Ilka; Hübschmann, Daniel; Kaderali, Lars; Cox, Jürgen; Brüne, Bernhard; Röllig, Christoph; Thiede, Christian; Steffen, Björn; Bornhäuser, Martin; Trumpp, Andreas; Urlaub, Henning; Stegmaier, Kimberly; Serve, Hubert; Mann, Matthias; Oellerich, Thomas.
Afiliação
  • Jayavelu AK; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany; Clinical Cooperation Unit Pediatric Leukemia, DKFZ and Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany; Hopp Children's Cancer Center Heidelber
  • Wolf S; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany.
  • Buettner F; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany.
  • Alexe G; Division of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
  • Häupl B; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute, Goethe U
  • Comoglio F; enGene Statistics GmbH, Basel, Switzerland.
  • Schneider C; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Doebele C; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Fuhrmann DC; Department of Biochemistry I, Goethe University, Frankfurt, Germany.
  • Wagner S; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Donato E; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.
  • Andresen C; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.
  • Wilke AC; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Zindel A; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Jahn D; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Splettstoesser B; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
  • Plessmann U; Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
  • Münch S; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Abou-El-Ardat K; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Makowka P; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Acker F; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Enssle JC; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Cremer A; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Schnütgen F; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute, Goethe U
  • Kurrle N; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute, Goethe U
  • Chapuy B; Department of Medical Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany; Department of Hematology, Oncology and Tumor Immunology, Charité, Campus Benjamin Franklin, University Medicine Berlin, Berlin, Germany.
  • Löber J; Department of Medical Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany; Department of Hematology, Oncology and Tumor Immunology, Charité, Campus Benjamin Franklin, University Medicine Berlin, Berlin, Germany.
  • Hartmann S; Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.
  • Wild PJ; Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany.
  • Wittig I; Functional Proteomics, Institute of Cardiovascular Physiology, Goethe University, Frankfurt, Germany.
  • Hübschmann D; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Pattern Recognition and Digital Medicine, Heidelberg Institute for Stem C
  • Kaderali L; Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany.
  • Cox J; Computational Systems Biochemistry Research Group, Max Planck Institute of Biochemistry, Martinsried, Germany.
  • Brüne B; Department of Biochemistry I, Goethe University, Frankfurt, Germany.
  • Röllig C; Department of Internal Medicine I, University Hospital Carl Gustav Carus TU Dresden, Dresden, Germany.
  • Thiede C; Department of Internal Medicine I, University Hospital Carl Gustav Carus TU Dresden, Dresden, Germany.
  • Steffen B; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany.
  • Bornhäuser M; Department of Internal Medicine I, University Hospital Carl Gustav Carus TU Dresden, Dresden, Germany; National Center for Tumor Diseases, Dresden (NCT/UCC), Dresden, Germany.
  • Trumpp A; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Urlaub H; Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany; Bioanalytics, Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
  • Stegmaier K; Division of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Serve H; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute, Goethe U
  • Mann M; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. Electronic address: mmann@biochem.mpg.de.
  • Oellerich T; Department of Medicine II, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute, Goethe U
Cancer Cell ; 40(3): 301-317.e12, 2022 03 14.
Article em En | MEDLINE | ID: mdl-35245447
Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing. We identify five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these proteomic subtypes correlate with patient outcome, but none is exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is captured only in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival on treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired toward stronger complex I-dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Leucemia Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Proteogenômica Limite: Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Leucemia Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Proteogenômica Limite: Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article