Proteomics

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The Proteogenomic Subtypes of Acute Myeloid Leukemia


ABSTRACT: Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. We performed 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 included cytogenetic and mutation profiling, and RNA sequencing. This identified five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these subtypes were correlated with patient outcome, but none exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which was only captured in the proteome, was characterized by high expression of mitochondrial proteins and showed poor outcome, with reduced remission rate and shorter overall survival upon treatment with intensive induction chemotherapy. Functional analyses revealed that Mito-AML is metabolically wired towards stronger complex Idependent respiration and is more responsive to treatment with the BCL2-inhibitor venetoclax.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Bone Marrow

SUBMITTER: Ashokkumar Jayavelu  

LAB HEAD: Prof.Matthias Mann

PROVIDER: PXD028007 | Pride | 2022-03-08

REPOSITORIES: pride

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Publications

The proteogenomic subtypes of acute myeloid leukemia.

Jayavelu Ashok Kumar AK   Wolf Sebastian S   Buettner Florian F   Alexe Gabriela G   Häupl Björn B   Comoglio Federico F   Schneider Constanze C   Doebele Carmen C   Fuhrmann Dominik C DC   Wagner Sebastian S   Donato Elisa E   Andresen Carolin C   Wilke Anne C AC   Zindel Alena A   Jahn Dominique D   Splettstoesser Bianca B   Plessmann Uwe U   Münch Silvia S   Abou-El-Ardat Khali K   Makowka Philipp P   Acker Fabian F   Enssle Julius C JC   Cremer Anjali A   Schnütgen Frank F   Kurrle Nina N   Chapuy Björn B   Löber Jens J   Hartmann Sylvia S   Wild Peter J PJ   Wittig Ilka I   Hübschmann Daniel D   Kaderali Lars L   Cox Jürgen J   Brüne Bernhard B   Röllig Christoph C   Thiede Christian C   Steffen Björn B   Bornhäuser Martin M   Trumpp Andreas A   Urlaub Henning H   Stegmaier Kimberly K   Serve Hubert H   Mann Matthias M   Oellerich Thomas T  

Cancer cell 20220303 3


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 biologi  ...[more]

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