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  The proteogenomic subtypes of acute myeloid leukemia

Jayavelu, A. K., Wolf, S., Buettner, F., Alexe, G., Häupl, 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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Jayavelu, Ashok Kumar, Author
Wolf, Sebastian, Author
Buettner, Florian, Author
Alexe, Gabriela, Author
Häupl, Björn, Author
Comoglio, Federico, Author
Schneider, Constanze, Author
Doebele, Carmen, Author
Fuhrmann, Dominik C., Author
Wagner, Sebastian, Author
Donato, Elisa, Author
Andresen, Carolin, Author
Wilke, Anne C., Author
Zindel, Alena, Author
Jahn, Dominique, Author
Splettstoesser, Bianca, Author
Plessmann, U.1, Author           
Münch, Silvia, Author
Abou-El-Ardat, Khali, Author
Makowka, Philipp, Author
Acker, Fabian, AuthorEnssle, Julius C., AuthorCremer, Anjali, AuthorSchnütgen, Frank, AuthorKurrle, Nina, AuthorChapuy, Björn, AuthorLöber, Jens, AuthorHartmann, Sylvia, AuthorWild, Peter J., AuthorWittig, Ilka, AuthorHübschmann, Daniel, AuthorKaderali, Lars, AuthorCox, Jürgen, AuthorBrüne, Bernhard, AuthorRöllig, Christoph, AuthorThiede, Christian, AuthorSteffen, Björn, AuthorBornhäuser, Martin, AuthorTrumpp, Andreas, AuthorUrlaub, Henning1, Author           Stegmaier, Kimberly, AuthorServe, Hubert, AuthorMann, Matthias, AuthorOellerich, Thomas, Author more..
1Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350290              


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 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.


Language(s): eng - English
 Dates: 2022
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.ccell.2022.02.006
 Degree: -



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Project name : We thank H. Lang, S. Mohr, and D. Yepes from the Oellerich laboratory and M. Sohn from the Trumpp laboratory for their technical support. We thank all the members of Proteomics and Signal Transduction Department at the Max Planck Institute for Biochemistry, particularly I. Paron, C. Deiml, J. Müller, G. Sowa, N. Nagaraj, and F. Meier for their technical assistance. We thank the staff of the University Cancer Center (UCT) and the Study Alliance Leukemia (SAL) biobanks for the close collaboration, particularly K. Götze, S. Jordan, M. Berger, and H. Altmann. Genomic sequencing was in parts done by MLL Dx, Munich and we thank particularly T. Haferlach, M. Meggendorfer and N. Nadarajah for expert technical assistance. A.K.J., B.Splettstoesser, and M.M. were supported by the Max Planck Society for the Advancement of Science and by the German Research Foundation (DFG/Gottfried Wilhelm Leibniz Prize). T.O. was supported by the German Research Foundation. S.Wolf was supported by the Else Kröner-Fresenius-Stiftung and the Mildred-Scheel-Nachwuchszentrum (MSNZ, German Cancer Aid). K.S. was supported by NIH R35 CA210030 and NIH P50 CA206963. This work was supported by SPP2036, FOR2674, and SFB873 funded by the Deutsche Forschungsgemeinschaft (DFG); the DKTK joint funding project “RiskY-AML”; and the Dietmar Hopp Foundation (all to A.T.). The graphical abstract was created by Dorotea Fracchiolla, Art&Science.
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Source 1

Title: Cancer Cell
  Other : Cancer Cell
Source Genre: Journal
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