Delineating functional and molecular impact of ex vivo sample handling in precision medicine.

Autor: Struyf N; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden. nona.struyf@ki.se., Österroos A; Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden., Vesterlund M; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Arnroth C; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., James T; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Sunandar S; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Mermelekas G; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Bohlin A; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden., Hamberg Levedahl K; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden., Bengtzén S; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden., Jafari R; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Orre LM; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Lehtiö J; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Lehmann S; Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden., Östling P; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Kallioniemi O; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., Seashore-Ludlow B; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden., Erkers T; Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden. tom.erkers@ki.se.
Jazyk: angličtina
Zdroj: NPJ precision oncology [NPJ Precis Oncol] 2024 Feb 19; Vol. 8 (1), pp. 38. Date of Electronic Publication: 2024 Feb 19.
DOI: 10.1038/s41698-024-00528-7
Abstrakt: Consistent handling of samples is crucial for achieving reproducible molecular and functional testing results in translational research. Here, we used 229 acute myeloid leukemia (AML) patient samples to assess the impact of sample handling on high-throughput functional drug testing, mass spectrometry-based proteomics, and flow cytometry. Our data revealed novel and previously described changes in cell phenotype and drug response dependent on sample biobanking. Specifically, myeloid cells with a CD117 (c-KIT) positive phenotype decreased after biobanking, potentially distorting cell population representations and affecting drugs targeting these cells. Additionally, highly granular AML cell numbers decreased after freezing. Secondly, protein expression levels, as well as sensitivity to drugs targeting cell proliferation, metabolism, tyrosine kinases (e.g., JAK, KIT, FLT3), and BH3 mimetics were notably affected by biobanking. Moreover, drug response profiles of paired fresh and frozen samples showed that freezing samples can lead to systematic errors in drug sensitivity scores. While a high correlation between fresh and frozen for the entire drug library was observed, freezing cells had a considerable impact at an individual level, which could influence outcomes in translational studies. Our study highlights conditions where standardization is needed to improve reproducibility, and where validation of data generated from biobanked cohorts may be particularly important.
(© 2024. The Author(s).)
Databáze: MEDLINE
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