Paper - Review

DOI: 10.1016/j.ccell.2022.02.006

Graphical abstract

In brief

J. et al.
→ perform an integrated multi-omics approach
→ to elucidate the proteogenomic landscape ← of acute myeloid leukemia

5 proteomic AML subtypes
→ are identified
← each reflecting specific biological features

❗: Mito-AML
← one proteomic subtype
→ is characterized ← by high expression of mitochondrial proteins
→ shows poor outcome
→ is hyper-dependent ← on complex I-dependent respiration

Highlights

❗: proteomic characterization ← of acute myeloid leukemia blasts
← from 252 patients

❗: Identification ← of 5 proteomic AML subtypes
← with specific biological features

❗: Proteomics → reveals Mito-AML
← as a high-risk subtype
← ❌ not evident in genomics

❗: mito-AML → is hyper-sensitive
→ to drugs → targeting mitochondrial complex I

Summary

AML
→ is an aggressive blood cancer
← with a poor prognosis

Report
→ a comprehensive proteogenomic analysis ← of bone marrow biopsies
← from 252 uniformly treated AML patients
→ to elucidate the molecular pathophysiology of AML
→ to inform 1⃣ future diagnostic 2⃣ therapeutic approaches

The analysis
→ includes 1⃣ cytogenetic profiling 2⃣ DNA/RNA sequencing
→ to in-depth quantitative proteomics

❗: identify → 5 proteomic AML subtypes
→ each reflecting specific biological features ← spanning genomic boundaries

2 ← of these proteomic subtypes
→ correlated ← with patient outcome
None → is exclusively associated
← with specific genomic aberrations

Mito-AML
← which is captured only ← in the proteome
→ is characterized ← by high expression of mitochondrial proteins
→ confers poor outcome ← with 1⃣ reduced remission rate 2⃣ shorter overall survival
← on treatment ← with intensive induction chemotherapy

Mito-AML
→ is metabolically wired → toward stronger complex I-dependent respirations
→ is more responsive → to treatment ← with the BCL2 inhibitor venetoclax

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