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The proteogenomic subtypes of acute myeloid leukemia

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 ap...

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Main Authors: Jayavelu, Ashok Kumar (Author) , Wolf, Sebastian (Author) , Buettner, Florian (Author) , Alexe, Gabriela (Author) , Häupl, Björn (Author) , Comoglio, Federico (Author) , Schneider, Constanze (Author) , Döbele, Carmen (Author) , Fuhrmann, Dominik Christian (Author) , Wagner, Sebastian (Author) , Donato, Elisa (Author) , Andresen, Carolin (Author) , Wilke, Anne C. (Author) , Zindel, Alena (Author) , Jahn, Dominique (Author) , Splettstoesser, Bianca (Author) , Plessmann, Uwe (Author) , Münch, Silvia (Author) , Abou-El-Ardat, Khalil (Author) , Makowka, Philipp (Author) , Acker, Fabian (Author) , Enßle, Julius Christoph (Author) , Cremer, Anjali (Author) , Schnütgen, Frank (Author) , Kurrle, Nina Susanne (Author) , Chapuy, Björn (Author) , Löber, Jens (Author) , Hartmann, Sylvia (Author) , Wild, Peter Johannes (Author) , Wittig, Ilka (Author) , Hübschmann, Daniel (Author) , Kaderali, Lars (Author) , Cox, Jürgen (Author) , Brüne, Bernhard (Author) , Röllig, Christoph (Author) , Thiede, Christian (Author) , Steffen, Björn (Author) , Bornhäuser, Martin (Author) , Trumpp, Andreas (Author) , Urlaub, Henning (Author) , Stegmaier, Kimberly (Author) , Serve, Hubert (Author) , Mann, Matthias (Author) , Oellerich, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 3 March 2022
In: Cancer cell
Year: 2022, Volume: 40, Issue: 3, Pages: 301-317, e12
ISSN:1878-3686
DOI:10.1016/j.ccell.2022.02.006
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ccell.2022.02.006
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1535610822000587
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Author Notes:Ashok Kumar Jayavelu, Sebastian Wolf, Florian Buettner, Gabriela Alexe, Björn Häupl, Federico Comoglio, Constanze Schneider, Carmen Doebele, Dominik C. Fuhrmann, Sebastian Wagner, Elisa Donato, Carolin Andresen, Anne C. Wilke, Alena Zindel, Dominique Jahn, Bianca Splettstoesser, Uwe Plessmann, Silvia Münch, Khali Abou-El-Ardat, Philipp Makowka, Fabian Acker, Julius C. Enssle, Anjali Cremer, Frank Schnütgen, Nina Kurrle, Björn Chapuy, Jens Löber, Sylvia Hartmann, Peter J. Wild, Ilka Wittig, Daniel Hübschmann, Lars Kaderali, Jürgen Cox, Bernhard Brüne, Christoph Röllig, Christian Thiede, Björn Steffen, Martin Bornhäuser, Andreas Trumpp, Henning Urlaub, Kimberly Stegmaier, Hubert Serve, Matthias Mann, and Thomas Oellerich

MARC

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520 |a 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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