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Delineating functio...
Delineating functional and molecular impact of ex vivo sample handling in precision medicine
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- Struyf, Nona (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Österroos, Albin (author)
- Uppsala universitet,Hematologi
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- Vesterlund, Mattias (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Arnroth, Cornelia (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- James, Tojo (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Sunandar, Stephanie (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Mermelekas, Georgios (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Bohlin, Anna (author)
- Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden.
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- Hamberg Levedahl, Kerstin (author)
- Uppsala universitet,Vårdvetenskap
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- Bengtzén, Sofia (author)
- Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden.
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- Jafari, Rozbeh (author)
- Karolinska Institutet
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- Orre, Lukas M. (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Lehtiö, Janne (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Lehmann, Sören (author)
- Uppsala universitet,Hematologi,Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden
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- Östling, Päivi (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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- Kallioniemi, Olli (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
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- Seashore-Ludlow, Brinton (author)
- Karolinska Institutet
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- Erkers, Tom (author)
- Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden.
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Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Stockholm, Sweden Hematologi (creator_code:org_t)
- Springer Nature, 2024
- 2024
- English.
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In: npj Precision Oncology. - : Springer Nature. - 2397-768X. ; 8:1
- Related links:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Struyf, Nona
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Österroos, Albin
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Vesterlund, Matt ...
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Arnroth, Corneli ...
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James, Tojo
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Sunandar, Stepha ...
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show more...
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Mermelekas, Geor ...
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Bohlin, Anna
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Hamberg Levedahl ...
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Bengtzén, Sofia
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Jafari, Rozbeh
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Orre, Lukas M.
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Lehtiö, Janne
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Lehmann, Sören
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Östling, Päivi
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Kallioniemi, Oll ...
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Seashore-Ludlow, ...
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Erkers, Tom
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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npj Precision On ...
- By the university
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Uppsala University
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Karolinska Institutet