{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:23:33Z","timestamp":1792596213804,"version":"4.5.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","award":["TJ2021-0080"],"award-info":[{"award-number":["TJ2021-0080"]}],"id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","award":["2020-01091"],"award-info":[{"award-number":["2020-01091"]}],"id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","award":["2018-02283"],"award-info":[{"award-number":["2018-02283"]}],"id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001729","name":"Stiftelsen f\u00f6r Strategisk Forskning","doi-asserted-by":"publisher","award":["SB16-0058"],"award-info":[{"award-number":["SB16-0058"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2017-06095"],"award-info":[{"award-number":["2017-06095"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["2015.0291"],"award-info":[{"award-number":["2015.0291"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Precis. Onc."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1038\/s41698-024-00528-7","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T13:02:11Z","timestamp":1708347731000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Delineating functional and molecular impact of ex vivo sample handling in precision medicine"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6975-0753","authenticated-orcid":false,"given":"Nona","family":"Struyf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-7299","authenticated-orcid":false,"given":"Albin","family":"\u00d6sterroos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9471-6592","authenticated-orcid":false,"given":"Mattias","family":"Vesterlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Arnroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tojo","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Sunandar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Mermelekas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bohlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Hamberg Levedahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Bengtz\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3396-4709","authenticated-orcid":false,"given":"Rozbeh","family":"Jafari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0384-1003","authenticated-orcid":false,"given":"Lukas M.","family":"Orre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Lehti\u00f6","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6ren","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"\u00d6stling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Kallioniemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-5967","authenticated-orcid":false,"given":"Brinton","family":"Seashore-Ludlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2754-6287","authenticated-orcid":false,"given":"Tom","family":"Erkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"528_CR1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1158\/2159-8290.CD-21-0410","volume":"12","author":"D Malani","year":"2022","unstructured":"Malani, D. et al. Implementing a functional precision medicine tumor board for acute myeloid leukemia. Cancer Discov. 12, 388\u2013401 (2022).","journal-title":"Cancer Discov."},{"key":"528_CR2","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1158\/2159-8290.CD-21-0538","volume":"12","author":"C Kornauth","year":"2022","unstructured":"Kornauth, C. et al. Functional precision medicine provides clinical benefit in advanced aggressive hematologic cancers and identifies exceptional responders. Cancer Discov. 12, 372\u2013387 (2022).","journal-title":"Cancer Discov."},{"key":"528_CR3","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nrc4015","volume":"15","author":"AA Friedman","year":"2015","unstructured":"Friedman, A. A., Letai, A., Fisher, D. E. & Flaherty, K. T. Precision medicine for cancer with next-generation functional diagnostics. Nat. Rev. Cancer 15, 747\u2013756 (2015).","journal-title":"Nat. Rev. Cancer"},{"key":"528_CR4","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1182\/blood.2022016867","volume":"140","author":"H D\u00f6hner","year":"2022","unstructured":"D\u00f6hner, H. et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140, 1345\u20131377 (2022).","journal-title":"Blood"},{"key":"528_CR5","doi-asserted-by":"publisher","first-page":"E5","DOI":"10.1038\/nature20171","volume":"540","author":"JP Mpindi","year":"2016","unstructured":"Mpindi, J. P. et al. Consistency in drug response profiling. Nature 540, E5\u2013E6 (2016).","journal-title":"Nature"},{"key":"528_CR6","doi-asserted-by":"publisher","first-page":"100730","DOI":"10.1016\/j.drup.2020.100730","volume":"53","author":"DGJ Cucchi","year":"2020","unstructured":"Cucchi, D. G. J., Groen, R. W. J., Janssen, J. & Cloos, J. Ex vivo cultures and drug testing of primary acute myeloid leukemia samples: current techniques and implications for experimental design and outcome. Drug Resist Updat. 53, 100730 (2020).","journal-title":"Drug Resist Updat"},{"key":"528_CR7","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ccell.2021.12.004","volume":"40","author":"A Letai","year":"2022","unstructured":"Letai, A., Bhola, P. & Welm, A. L. Functional precision oncology: testing tumors with drugs to identify vulnerabilities and novel combinations. Cancer Cell 40, 26\u201335 (2022).","journal-title":"Cancer Cell"},{"key":"528_CR8","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/108705719900400206","volume":"4","author":"JH Zhang","year":"1999","unstructured":"Zhang, J. H., Chung, T. D. & Oldenburg, K. R. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J. Biomol. Screen 4, 67\u201373 (1999).","journal-title":"J. Biomol. Screen"},{"key":"528_CR9","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.2174\/13816128113199990593","volume":"20","author":"K Stankov","year":"2014","unstructured":"Stankov, K., Popovic, S. & Mikov, M. C-KIT signaling in cancer treatment. Curr. Pharm. Des. 20, 2849\u20132880 (2014).","journal-title":"Curr. Pharm. Des."},{"key":"528_CR10","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.2147\/DDDT.S89114","volume":"10","author":"M Abbaspour Babaei","year":"2016","unstructured":"Abbaspour Babaei, M., Kamalidehghan, B., Saleem, M., Huri, H. Z. & Ahmadipour, F. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des. Dev. Ther. 10, 2443\u20132459 (2016).","journal-title":"Drug Des. Dev. Ther."},{"key":"528_CR11","doi-asserted-by":"publisher","first-page":"e595","DOI":"10.1016\/S2352-3026(17)30208-9","volume":"4","author":"B Snijder","year":"2017","unstructured":"Snijder, B. et al. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study. Lancet Haematol. 4, e595\u2013e606 (2017).","journal-title":"Lancet Haematol."},{"key":"528_CR12","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/978-1-59745-362-2_20","volume":"368","author":"A Sputtek","year":"2007","unstructured":"Sputtek, A. Cryopreservation of red blood cells and platelets. Methods Mol. Biol. 368, 283\u2013301 (2007).","journal-title":"Methods Mol. Biol."},{"key":"528_CR13","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1158\/2159-8290.CD-19-0125","volume":"9","author":"T Nechiporuk","year":"2019","unstructured":"Nechiporuk, T. et al. The TP53 apoptotic network is a primary mediator of resistance to BCL2 inhibition in AML cells. Cancer Discov. 9, 910\u2013925 (2019).","journal-title":"Cancer Discov."},{"key":"528_CR14","doi-asserted-by":"publisher","first-page":"eabm9427","DOI":"10.1126\/sciadv.abm9427","volume":"8","author":"KM Fujihara","year":"2022","unstructured":"Fujihara, K. M. et al. Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction. Sci. Adv. 8, eabm9427 (2022).","journal-title":"Sci. Adv."},{"key":"528_CR15","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/s41418-022-00943-y","volume":"29","author":"Y Liu","year":"2022","unstructured":"Liu, Y. & Gu, W. p53 in ferroptosis regulation: the new weapon for the old guardian. Cell Death Differ. 29, 895\u2013910 (2022).","journal-title":"Cell Death Differ."},{"key":"528_CR16","doi-asserted-by":"publisher","first-page":"e359","DOI":"10.1097\/MPH.0000000000000946","volume":"39","author":"M Degnin","year":"2017","unstructured":"Degnin, M. et al. Novel method enabling the use of cryopreserved primary acute myeloid leukemia cells in functional drug screens. J. Pediatr. Hematol. Oncol. 39, e359\u2013e366 (2017).","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"528_CR17","first-page":"e32","volume":"3","author":"N Meszaros","year":"2023","unstructured":"Meszaros, N. et al. Influence of cryopreservation on drug responses and gene expression of AML cells: Implications for the use of biobanked tissues. Br. J. Haematol. 3, e32\u2013e36 (2023).","journal-title":"Br. J. Haematol."},{"key":"528_CR18","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1021\/acs.jproteome.7b00913","volume":"17","author":"S Moggridge","year":"2018","unstructured":"Moggridge, S., Sorensen, P. H., Morin, G. B. & Hughes, C. S. Extending the compatibility of the SP3 paramagnetic bead processing approach for proteomics. J. Proteome Res. 17, 1730\u20131740 (2018).","journal-title":"J. Proteome Res"},{"key":"528_CR19","doi-asserted-by":"publisher","first-page":"757","DOI":"10.15252\/msb.20145625","volume":"10","author":"CS Hughes","year":"2014","unstructured":"Hughes, C. S. et al. Ultrasensitive proteome analysis using paramagnetic bead technology. Mol. Syst. Biol. 10, 757 (2014).","journal-title":"Mol. Syst. Biol."},{"key":"528_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04279-5","volume":"9","author":"Y Zhu","year":"2018","unstructured":"Zhu, Y. et al. Publisher correction: discovery of coding regions in the human genome by integrated proteogenomics analysis workflow. Nat. Commun. 9, 1852 (2018).","journal-title":"Nat. Commun."},{"key":"528_CR21","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nmeth.2732","volume":"11","author":"RM Branca","year":"2014","unstructured":"Branca, R. M. et al. HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics. Nat. Methods 11, 59\u201362 (2014).","journal-title":"Nat. Methods"},{"key":"528_CR22","doi-asserted-by":"publisher","first-page":"13 24 1","DOI":"10.1002\/0471250953.bi1324s46","volume":"46","author":"JD Holman","year":"2014","unstructured":"Holman, J. D., Tabb, D. L. & Mallick, P. Employing proteowizard to convert raw mass spectrometry data. Curr. Protoc. Bioinform. 46, 13 24 1\u201313 24 9 (2014).","journal-title":"Curr. Protoc. Bioinform."},{"key":"528_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6277","volume":"5","author":"S Kim","year":"2014","unstructured":"Kim, S. & Pevzner, P. A. MS-GF+ makes progress towards a universal database search tool for proteomics. Nat. Commun. 5, 5277 (2014).","journal-title":"Nat. Commun."},{"key":"528_CR24","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1021\/pr400937n","volume":"13","author":"V Granholm","year":"2014","unstructured":"Granholm, V. et al. Fast and accurate database searches with MS-GF+Percolator. J. Proteome Res. 13, 890\u2013897 (2014).","journal-title":"J. Proteome Res"},{"key":"528_CR25","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/nbt.3134","volume":"33","author":"J Boekel","year":"2015","unstructured":"Boekel, J. et al. Multi-omic data analysis using Galaxy. Nat. Biotechnol. 33, 137\u2013139 (2015).","journal-title":"Nat. Biotechnol."},{"key":"528_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-163","volume":"9","author":"M Sturm","year":"2008","unstructured":"Sturm, M. et al. OpenMS\u2014an open-source software framework for mass spectrometry. BMC Bioinform. 9, 163 (2008).","journal-title":"BMC Bioinform."},{"key":"528_CR27","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1074\/mcp.M114.046995","volume":"14","author":"MM Savitski","year":"2015","unstructured":"Savitski, M. M., Wilhelm, M., Hahne, H., Kuster, B. & Bantscheff, M. A scalable approach for protein false discovery rate estimation in large proteomic data sets. Mol. Cell Proteom. 14, 2394\u20132404 (2015).","journal-title":"Mol. Cell Proteom."},{"key":"528_CR28","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1158\/2159-8290.CD-13-0350","volume":"3","author":"T Pemovska","year":"2013","unstructured":"Pemovska, T. et al. Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov. 3, 1416\u20131429 (2013).","journal-title":"Cancer Discov."},{"key":"528_CR29","doi-asserted-by":"publisher","first-page":"3602","DOI":"10.1093\/bioinformatics\/btaa138","volume":"36","author":"S Potdar","year":"2020","unstructured":"Potdar, S. et al. Breeze: an integrated quality control and data analysis application for high-throughput drug screening. Bioinformatics 36, 3602\u20133604 (2020).","journal-title":"Bioinformatics"},{"key":"528_CR30","unstructured":"Morpheus. https:\/\/software.broadinstitute.org\/morpheus."},{"key":"528_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v057.i12","volume":"57","author":"I Subirana","year":"2014","unstructured":"Subirana, I., Sanz, H. & Vila, J. Building bivariate tables: the compareGroups package for R. J. Stat. Softw. 57, 1\u201316 (2014). 05\/06.","journal-title":"J. Stat. Softw."},{"key":"528_CR32","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43, e47 (2015).","journal-title":"Nucleic Acids Res"},{"key":"528_CR33","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284\u2013287 (2012).","journal-title":"OMICS"}],"container-title":["npj Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41698-024-00528-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-024-00528-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-024-00528-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T13:22:08Z","timestamp":1708348928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41698-024-00528-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,19]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["528"],"URL":"https:\/\/doi.org\/10.1038\/s41698-024-00528-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3072667\/v1","asserted-by":"object"}]},"ISSN":["2397-768X"],"issn-type":[{"value":"2397-768X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,19]]},"assertion":[{"value":"16 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The author O.K. is a co-founder and a board member of Sartar Therapeutics and has received royalty on patents licensed by Vysis-Abbot. None of the other authors have any conflicts of interest to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38"}}