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  • Struyf, NonaKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)

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

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • Springer Nature,2024
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-524603
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524603URI
  • https://doi.org/10.1038/s41698-024-00528-7DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:155022906URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Österroos, AlbinUppsala universitet,Hematologi(Swepub:uu)albos903 (author)
  • Vesterlund, MattiasKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Arnroth, CorneliaKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • James, TojoKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Sunandar, StephanieKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Mermelekas, GeorgiosKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Bohlin, AnnaKarolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden. (author)
  • Hamberg Levedahl, KerstinUppsala universitet,Vårdvetenskap(Swepub:uu)kerle139 (author)
  • Bengtzén, SofiaKarolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden. (author)
  • Jafari, RozbehKarolinska Institutet (author)
  • Orre, Lukas M.Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Lehtiö, JanneKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Lehmann, SörenUppsala universitet,Hematologi,Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden(Swepub:uu)sorle534 (author)
  • Östling, PäiviKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Kallioniemi, OlliKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. (author)
  • Seashore-Ludlow, BrintonKarolinska Institutet (author)
  • Erkers, TomKarolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden. (author)
  • Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.Hematologi (creator_code:org_t)

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