{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:31:23Z","timestamp":1775932283964,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["FNBr 65269705"],"award-info":[{"award-number":["FNBr 65269705"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NU\u201020\u201008\u201000314"],"award-info":[{"award-number":["NU\u201020\u201008\u201000314"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["23\u201005561S"],"award-info":[{"award-number":["23\u201005561S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011659","name":"L\u00e9ka\u0159sk\u00e1 fakulta, Masarykova univerzita","doi-asserted-by":"publisher","award":["MUNI\/A\/1558\/2023"],"award-info":[{"award-number":["MUNI\/A\/1558\/2023"]}],"id":[{"id":"10.13039\/501100011659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"abstract":"<jats:p>\n                    Early identification of resistant cancer cells is currently a major challenge, as their expansion leads to refractoriness. To capture the dynamics of these cells, we made a comprehensive analysis of disease progression and treatment response in a chronic lymphocytic leukemia (CLL) patient using a combination of single\u2010cell and bulk genomic methods. At diagnosis, the patient presented with unfavorable genetic markers, including notch receptor 1 (\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    ) mutation and loss(11q). The initial and subsequent treatment lines did not lead to a durable response and the patient developed refractory disease. Refractory CLL cells featured substantial dysregulation in B\u2010cell phenotypic markers such as human leukocyte antigen (HLA) genes, immunoglobulin (IG) genes, CD19 molecule (\n                    <jats:italic>CD19<\/jats:italic>\n                    ), membrane spanning 4\u2010domains A1 (\n                    <jats:italic>MS4A1<\/jats:italic>\n                    ; previously known as CD20), CD79a molecule (\n                    <jats:italic>CD79A<\/jats:italic>\n                    ) and paired box 5 (\n                    <jats:italic>PAX5<\/jats:italic>\n                    ), indicating B\u2010cell de\u2010differentiation and disease transformation. We described the clonal evolution and characterized in detail two cell populations that emerged during the refractory disease phase, differing in the presence of high genomic complexity. In addition, we successfully tracked the cells with high genomic complexity back to the time before treatment, where they formed a rare subpopulation. We have confirmed that single\u2010cell RNA sequencing enables the characterization of refractory cells and the monitoring of their development over time.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13663","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T03:39:30Z","timestamp":1716262770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unveiling the dynamics and molecular landscape of a rare chronic lymphocytic leukemia subpopulation driving refractoriness: insights from single\u2010cell\n                    <scp>RNA<\/scp>\n                    sequencing"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7110-5543","authenticated-orcid":false,"given":"Terezia","family":"Kurucova","sequence":"first","affiliation":[{"name":"Central European Institute of Technology, Center of Molecular Medicine Masaryk University  Brno Czech Republic"},{"name":"Department of Experimental Biology, Faculty of Science Masaryk University  Brno Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6453-2386","authenticated-orcid":false,"given":"Kamila","family":"Reblova","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Center of Molecular Medicine Masaryk University  Brno Czech Republic"},{"name":"Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9871-0876","authenticated-orcid":false,"given":"Pavlina","family":"Janovska","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Faculty of Science Masaryk University  Brno Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0269-4370","authenticated-orcid":false,"given":"Jakub Pawel","family":"Porc","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Center of Molecular Medicine Masaryk University  Brno Czech Republic"},{"name":"Institute of Medical Genetics and Genomics, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3020-1578","authenticated-orcid":false,"given":"Veronika","family":"Navrkalova","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Center of Molecular Medicine Masaryk University  Brno Czech Republic"},{"name":"Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"},{"name":"Institute of Medical Genetics and Genomics, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1528-9743","authenticated-orcid":false,"given":"Sarka","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Center of Molecular Medicine Masaryk University  Brno Czech Republic"},{"name":"Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"},{"name":"Institute of Medical Genetics and Genomics, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3650-6698","authenticated-orcid":false,"given":"Jitka","family":"Malcikova","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Center of Molecular Medicine Masaryk University  Brno Czech Republic"},{"name":"Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"},{"name":"Institute of Medical Genetics and Genomics, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6148-8877","authenticated-orcid":false,"given":"Karla","family":"Plevova","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Center of Molecular Medicine Masaryk University  Brno Czech Republic"},{"name":"Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University and University Hospital Brno  Czech Republic"},{"name":"Institute of Medical Genetics and Genomics, Faculty of Medicine Masaryk University and University Hospital Brno  Czech 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