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The Proteogenomic Subtypes of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an aggressive blood cancer with 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 are exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is only captured in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival upon treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired towards stronger complex I dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001008484 Illumina NovaSeq 6000 177
EGAD00001008485 Illumina NovaSeq 6000 15
EGAD00001008488 NextSeq 550 1
EGAD00001008501 NextSeq 500 19
EGAD00001008506 -
Publications Citations
Preleukemic single-cell landscapes reveal mutation-specific mechanisms and gene programs predictive of AML patient outcomes.
Cell Genom 3: 2023 100426