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  The proteogenomic subtypes of acute myeloid leukemia

Jayavelu, A. K., Wolf, S., Buettner, F., Alexe, G., Haeupl, B., Comoglio, F., et al. (2022). The proteogenomic subtypes of acute myeloid leukemia. Cancer Cell, 40(3), 301-317.e12. doi:10.1016/j.ccell.2022.02.006.

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 Creators:
Jayavelu, Ashok Kumar1, Author              
Wolf, Sebastian2, Author
Buettner, Florian2, Author
Alexe, Gabriela2, Author
Haeupl, Bjoern2, Author
Comoglio, Federico2, Author
Schneider, Constanze2, Author
Doebele, Carmen2, Author
Fuhrmann, Dominik C.2, Author
Wagner, Sebastian2, Author
Donato, Elisa2, Author
Andresen, Carolin2, Author
Wilke, Anne C.2, Author
Zindel, Alena2, Author
Jahn, Dominique2, Author
Splettstoesser, Bianca1, Author              
Plessmann, Uwe2, Author
Muench, Silvia2, Author
Abou-El-Ardat, Khali2, Author
Makowka, Philipp2, Author
Acker, Fabian2, AuthorEnssle, Julius C.2, AuthorCremer, Anjali2, AuthorSchnutgen, Frank2, AuthorKurrle, Nina2, AuthorChapuy, Bjoern2, AuthorLoeber, Jens2, AuthorHartmann, Sylvia2, AuthorWild, Peter J.2, AuthorWittig, Ilka2, AuthorHuebschmann, Daniel2, AuthorKaderali, Lars2, AuthorCox, Juergen3, Author              Bruene, Bernhard2, AuthorRoellig, Christoph2, AuthorThiede, Christian2, AuthorSteffen, Bjoern2, AuthorBornhaeuser, Martin2, AuthorTrumpp, Andreas2, AuthorUrlaub, Henning2, AuthorStegmaier, Kimberly2, AuthorServe, Hubert2, AuthorMann, Matthias1, Author              Oellerich, Thomas2, Author more..
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              
3Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_2063284              

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Free keywords: ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION; FUNCTIONAL PREDICTIONS; COMPUTATIONAL PLATFORM; DATABASE; PROTEIN; HETEROGENEITY; AML; CLASSIFICATION; IDENTIFICATIONOncology; Cell Biology;
 Abstract: 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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Language(s): eng - English
 Dates: 2022
 Publication Status: Published in print
 Pages: 30
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Cancer Cell
  Other : Cancer Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 40 (3) Sequence Number: - Start / End Page: 301 - 317.e12 Identifier: ISSN: 1535-6108
CoNE: https://pure.mpg.de/cone/journals/resource/111025129473004