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One memory (CD27\n                    <jats:sup>+<\/jats:sup>\n                    CD38\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) and two na\u00efve (CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD38\n                    <jats:sup>+<\/jats:sup>\n                    ) CD19\n                    <jats:sup>+<\/jats:sup>\n                    clusters with a non-malignant phenotype (NMP; CD5\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD43\n                    <jats:sup>\u2212<\/jats:sup>\n                    ROR1\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD20\n                    <jats:sup>hi<\/jats:sup>\n                    CD79b\n                    <jats:sup>hi<\/jats:sup>\n                    CD81\n                    <jats:sup>+<\/jats:sup>\n                    ) were identified by FlowSOM and UMAP algorithms. NMP clusters were most prevalent in healthy controls, almost undetectable in untreated and relapsed CLL, and variable following CIT, where they correlated with haematopoietic recovery (na\u00efve NMP clusters) and polyclonal antibody production (memory NMP cluster). Larger NMP cluster size at the early post-treatment timepoint was associated with a significantly longer progression free survival (PFS; HR 0.40 [95% CI: 0.22\u20130.75];\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.003). Similar findings were obtained when NMBCs were prospectively defined by Boolean gating using the non-redundant features of the NMP clusters. NMBCs measured in this way negatively correlated with MRD and provided complementary prognostic information in patients with persistent MRD. Our findings raise the possibility that re-emergence of circulating NMBCs after treatment reflects clearance of CLL from secondary lymphoid organs, thereby complementing MRD as a biomarker of bone marrow clearance.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-16558-5","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T10:56:01Z","timestamp":1758884161000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Re-emergence of circulating non-malignant B cells as a prognostic biomarker in chronic lymphocytic leukaemia"],"prefix":"10.1038","volume":"15","author":[{"given":"Yeong Jer","family":"Lim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Duckworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Oates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indrani","family":"Karpha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Gornall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagesh","family":"Kalakonda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Slupsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Pettitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"issue":"5","key":"16558_CR1","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1182\/blood-2015-03-567388","volume":"126","author":"F Forconi","year":"2015","unstructured":"Forconi, F. & Moss, P. 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NK has sat on advisory boards for BMS\/Celgene, Gilead\/Kite, Hospira, Incyte\/Morphosys, Janssen, Karyopharm, Roche, Takeda; and received research funding from BMS\/Celgene, Gilead\/Kite and Roche. All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Research Ethics Committee (REC) approvals were obtained for the collection and analysis of of CLL patients (REC ref. 19\/NW\/0573) and healthy controls (REC ref. 16\/NW\/0810). The study was performed in accordance with the Declaration of Helsinki and relevant ethical guidelines for research in humans, with written consent obtained from all patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"33072"}}