Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 14;40(3):301-317.e12.
doi: 10.1016/j.ccell.2022.02.006. Epub 2022 Mar 3.

The proteogenomic subtypes of acute myeloid leukemia

Ashok Kumar Jayavelu  1 , Sebastian Wolf  2 , Florian Buettner  3 , Gabriela Alexe  4 , Björn Häupl  5 , Federico Comoglio  6 , Constanze Schneider  7 , Carmen Doebele  8 , Dominik C Fuhrmann  9 , Sebastian Wagner  7 , Elisa Donato  10 , Carolin Andresen  10 , Anne C Wilke  7 , Alena Zindel  8 , Dominique Jahn  8 , Bianca Splettstoesser  11 , Uwe Plessmann  12 , Silvia Münch  7 , Khali Abou-El-Ardat  7 , Philipp Makowka  7 , Fabian Acker  7 , Julius C Enssle  7 , Anjali Cremer  7 , Frank Schnütgen  5 , Nina Kurrle  5 , Björn Chapuy  13 , Jens Löber  13 , Sylvia Hartmann  14 , Peter J Wild  14 , Ilka Wittig  15 , Daniel Hübschmann  16 , Lars Kaderali  17 , Jürgen Cox  18 , Bernhard Brüne  9 , Christoph Röllig  19 , Christian Thiede  19 , Björn Steffen  7 , Martin Bornhäuser  20 , Andreas Trumpp  21 , Henning Urlaub  22 , Kimberly Stegmaier  23 , Hubert Serve  24 , Matthias Mann  25 , Thomas Oellerich  26
Affiliations
Free article

The proteogenomic subtypes of acute myeloid leukemia

Ashok Kumar Jayavelu et al. Cancer Cell. .
Free article

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.

Keywords: BCL-2 inhibitor; acute myeloid leukemia; chemotherapy; mitochondrial oxidative phosphorylation; multi-omics data integration; proteogenomics; proteomics; venetoclax.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests T.O. received research funding from Gilead (related to this work) and Merck KGaA (not related to this work). T.O. is a consultant for Roche and Merck KGaA (both not related to this work). K.S. receives grant funding as part of the DFCI/Novartis Drug Discovery Program, consults for and has stock options in Auron Therapeutics, and has consulted for Kronos Bio and AstraZeneca on topics not directly related to this manuscript. F.C. is a co-founder of enGene Statistics GmbH. The Max Planck institute and the Goethe University Frankfurt are filing a patent application, on which T.O., A.K.J., S.Wolf, F.B., H.S., M.M., and H.U. are listed as inventors.

Publication types