Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children.
Leukemia
; 37(3): 550-559, 2023 03.
Article
in En
| MEDLINE
| ID: mdl-36572751
ABSTRACT
Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Myeloid, Acute
/
Proteogenomics
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Child
/
Humans
Language:
En
Journal:
Leukemia
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2023
Type:
Article
Affiliation country:
Sweden