{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:24:06Z","timestamp":1787117046667,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["C45542\/A21705"],"award-info":[{"award-number":["C45542\/A21705"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"award":["C45542\/A21705"],"award-info":[{"award-number":["C45542\/A21705"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016131","name":"Howat Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100016131","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01b09k795","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Friends of Paul O\u2019Gorman and Beatson Cancer Charity"},{"id":[{"id":"https:\/\/ror.org\/02j37bn23","id-type":"ROR","asserted-by":"publisher"}]},{"name":"MRC DTP in Precision Medicine, University of Glasgow"},{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematol. Rep.","Hematology Reports"],"abstract":"<jats:p>Background\/Objectives: Revolutionary small molecule, targeted, tyrosine kinase inhibitors (TKIs) in the clinic have engendered the perception that optimal treatment has already been established for diseases like chronic myeloid leukemia (CML). Addressing BCR::ABL1 oncokinase domain mutations in CML is unlikely to redress disease recrudescence owing to persistent leukemia stem cells (LSCs). Therefore, it is necessary to consider an alternative strategic approach: disrupting LSC interactions with the protective microenvironment and\/or immune system. The interaction of the TNF-\u03b1 superfamily member, CD27, with its upregulated ligand, CD70, initiates survival signaling specifically in CML cells when BCR::ABL1 is inhibited by TKIs and thus represents an attractive target. Previous studies modulating the expression of CD27 on LSCs in a mouse model of advanced phase CML were encouraging. In our study, we explored the CD70\/CD27 axis as a therapeutic target in early-phase disease. Methods: Primitive CD34+ cells from treatment-na\u00efve chronic phase (CP) CML patients were drug-exposed in an in vitro co-culture system; combination drug treatments of the therapeutic anti-CD70 antibody and TKIs, nilotinib, were assessed in our CP CML murine model. Results: The blockade of the CD70\/CD27 axis in combination with TKIs did not result in greater LSC elimination than with nilotinib as a single agent in our CP CML models. Nonetheless, there was an observed reduction in CD70+ cells with combination treatment. Conclusion: Further preclinical study of the antibody as an adjunct in CD70-expressing hematological malignancy is perhaps warranted.<\/jats:p>","DOI":"10.3390\/hematolrep18040059","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:00:05Z","timestamp":1786964405000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The CD70\/CD27 Axis in Tyrosine Kinase Inhibitor-Treated Chronic Phase Chronic Myeloid Leukemia Cells Is Not an Achilles Heel"],"prefix":"10.3390","volume":"18","author":[{"given":"Jennifer","family":"Cassels","sequence":"first","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Drotar","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-2755","authenticated-orcid":false,"given":"Alyson","family":"MacNeil","sequence":"additional","affiliation":[{"name":"Centre for Healthcare Randomised Trials (CHaRT), Aberdeen Centre for Evaluation, Health Sciences Building, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Moles","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ching","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-1609","authenticated-orcid":false,"given":"Cassie J.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Scotland Institute, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Switchback Road, Glasgow G61 1BD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0933-8126","authenticated-orcid":false,"given":"Eoghan","family":"Forde","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Inflammation Research, Queen\u2019s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Jackson","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira A.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Scottish National Blood Transfusion Service, Jack Copland Centre, Currie, Edinburgh EH14 4BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Jacobs","sequence":"additional","affiliation":[{"name":"argenx BV, Industriepark Zwijnaarde 7, Zwijnaarde, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Zabrocki","sequence":"additional","affiliation":[{"name":"argenx BV, Industriepark Zwijnaarde 7, Zwijnaarde, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7655-016X","authenticated-orcid":false,"given":"Mhairi","family":"Copland","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9902-3170","authenticated-orcid":false,"given":"Helen","family":"Wheadon","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5404-475X","authenticated-orcid":false,"given":"Alison M.","family":"Michie","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4663-4191","authenticated-orcid":false,"given":"Heather G.","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Paul O\u2019Gorman Leukaemia Research Centre, School of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, 21 Shelley Road, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/243290a0","article-title":"A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and giemsa staining","volume":"243","author":"Rowley","year":"1973","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1126\/science.3460176","article-title":"The chronic myelogenous leukemia-specific P210 protein is the product of the bcr\/abl hybrid gene","volume":"233","author":"Daley","year":"1986","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0002-9343(77)90124-3","article-title":"Chronic myelocytic leukemia: Clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and 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