Open this publication in new window or tab >>Department of Clinical Medicine - Department of Pediatrics and Adolescent Medicine, Aarhus University, Denmark.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer Immunotherapy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Norwegian Institute of Public Health, Oslo, Norway; Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Department of Oncology and Pathology, Karolinska Institutet and Karolinska University hospital, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2023 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 37, no 3, p. 550-559Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Acute myeloid leukemia, proteomics, proteogenomics, relapse and resistance
National Category
Cancer and Oncology Hematology
Research subject
Biology with specialization in Molecular Biology
Identifiers
urn:nbn:se:uu:diva-427205 (URN)10.1038/s41375-022-01796-7 (DOI)000903999000001 ()36572751 (PubMedID)
Funder
Swedish Research Council, 2018-05973Swedish Research Council, 2013-03486Knut and Alice Wallenberg Foundation, 2013-03486Swedish Childhood Cancer Foundation, PR2013-0070Swedish Childhood Cancer Foundation, TJ2013-0045Swedish Cancer Society, CAN2013/489Kjell and Marta Beijer Foundation
Note
Title in the list of papers of Svea Stratmann thesis: Proteogenomic analysis of relapsed acute myeloid leukemia in adults and children
Authors in the list of papers of Svea Stramann: S. Stratmann, M. Vesterlund, H.M. Umer, A. Skaftason, M. Krogh Herlin, C. Sundström, A. Eriksson, M. Höglund, J. Palle, J. Abrahamson, K. Jahnukainen, M. Cheng Munthe-Kaas, B. Zeller, K. Pokrovskaja Tamm, L. Cavelier, J. Lehtiö, L. Holmfeld
2020-12-032020-12-032023-05-12Bibliographically approved