{"entity": "researcher", "timestamp": "2026-07-15T16:22:41.078Z", "family": "Woll", "given": "Petter S", "initials": "PS", "orcid": "0000-0002-2340-2526", "affiliations": ["Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden. petter.woll@ki.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68"}}, "publications": [{"entity": "publication", "iuid": "05f686d75d0343e0a27bd5e6fb686ba1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/05f686d75d0343e0a27bd5e6fb686ba1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/05f686d75d0343e0a27bd5e6fb686ba1"}}, "title": "Stable clonal contribution of lineage-restricted stem cells to human hematopoiesis.", "authors": [{"family": "Yoshizato", "given": "Tetsuichi", "initials": "T", "orcid": "0000-0003-4283-2983", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6f499e339d2444b817a81ab2712b9e5.json"}}, {"family": "Nilsson", "given": "Christer", "initials": "C", "orcid": "0000-0003-0695-0050", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f78180b33fa48cd86474d5c3cdaa852.json"}}, {"family": "Grasso", "given": "Francesca", "initials": "F"}, {"family": "H\u00f6gstrand", "given": "Kari", "initials": "K"}, {"family": "Mazzi", "given": "Stefania", "initials": "S", "orcid": "0009-0009-2676-5232", "researcher": {"href": "https://publications.scilifelab.se/researcher/83dc55ff218049b287e650588772cbfd.json"}}, {"family": "Winroth", "given": "Axel", "initials": "A", "orcid": "0009-0002-3314-7781", "researcher": {"href": "https://publications.scilifelab.se/researcher/63fae66620a04a79bb642b29703a5aaf.json"}}, {"family": "Lehander", "given": "Madeleine", "initials": "M"}, {"family": "Barbosa", "given": "Indira", "initials": "I", "orcid": "0009-0004-1171-2932", "researcher": {"href": "https://publications.scilifelab.se/researcher/20efd8770db84811a240a8bb70c43939.json"}}, {"family": "Waldin", "given": "Gunilla", "initials": "G"}, {"family": "Mortera-Blanco", "given": "Teresa", "initials": "T"}, {"family": "Jansson", "given": "Monika", "initials": "M"}, {"family": "Widfeldt", "given": "Mikaela Hillberg", "initials": "MH"}, {"family": "Aliouat", "given": "Affaf", "initials": "A"}, {"family": "Brennan", "given": "Margs S", "initials": "MS", "orcid": "0000-0002-8864-4147", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b684863566a420bb894bbd7265d938e.json"}}, {"family": "Markljung", "given": "Ellen", "initials": "E"}, {"family": "Hillen", "given": "Amy", "initials": "A", "orcid": "0000-0002-8567-1545", "researcher": {"href": "https://publications.scilifelab.se/researcher/fba7f6c5a2f04d71816a8381ede8a615.json"}}, {"family": "Chari", "given": "Edwin", "initials": "E"}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-7839-3743", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bf8d52e24234fa8b348ad08f58d1d48.json"}}, {"family": "Kretzschmar", "given": "Warren W", "initials": "WW", "orcid": "0000-0002-2575-0807", "researcher": {"href": "https://publications.scilifelab.se/researcher/a67389ef276a47cfacec7cbe50da37a7.json"}}, {"family": "Woll", "given": "Petter S", "initials": "PS", "orcid": "0000-0002-2340-2526", "researcher": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68.json"}}, {"family": "Jacobsen", "given": "Sten Eirik W", "initials": "SEW", "orcid": "0000-0002-1362-3659", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fc5e4f49e4330b095c26cd965cc98.json"}}], "type": "journal article", "published": "2025-11-11", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "issn-l": "1061-4036"}, "abstract": "Dynamic steady-state lineage contribution of human hematopoietic stem cell (HSC) clones needs to be assessed over time. However, clonal contribution of HSCs has only been investigated at single time points and without assessing the critical erythroid and platelet lineages. Here we screened for somatic mutations in healthy aged individuals, identifying expanded HSC clones accessible for lineage tracing of all major blood cell lineages. In addition to HSC clones with balanced contribution to all lineages, we identified clones with all myeloid lineages but no or few B and T lymphocytes or all myeloid lineages and B cells but no T cells. No other lineage restriction patterns were reproducibly observed. Retrospective phylogenetic inferences uncovered a 'hierarchical' pattern of descendant subclones more lineage biased than their ancestral clone and a more common 'stable' pattern with descendant subclones showing highly concordant lineage contributions with their ancestral clone, despite decades of separation. Prospective lineage tracing confirmed remarkable stability over years of HSC clones with distinct lineage replenishment patterns.", "doi": "10.1038/s41588-025-02405-w", "pmid": "41219528", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41588-025-02405-w"}], "notes": [], "created": "2025-11-21T14:18:19.115Z", "modified": "2025-11-21T14:18:20.018Z"}, {"entity": "publication", "iuid": "d95f4f6b8ceb4ca7b80714ec7fcb18f4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d95f4f6b8ceb4ca7b80714ec7fcb18f4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d95f4f6b8ceb4ca7b80714ec7fcb18f4"}}, "title": "Identification and surveillance of rare relapse-initiating stem cells during complete remission after transplantation.", "authors": [{"family": "Dimitriou", "given": "Marios", "initials": "M", "orcid": "0000-0001-8362-2099", "researcher": {"href": "https://publications.scilifelab.se/researcher/531c153359bb400fb48c7324a3bd69ad.json"}}, {"family": "Mortera-Blanco", "given": "Teresa", "initials": "T"}, {"family": "Tobiasson", "given": "Magnus", "initials": "M", "orcid": "0000-0002-3633-5852", "researcher": {"href": "https://publications.scilifelab.se/researcher/37b88e8e02af4145b95cc379c68ebee9.json"}}, {"family": "Mazzi", "given": "Stefania", "initials": "S"}, {"family": "Lehander", "given": "Madeleine", "initials": "M", "orcid": "0009-0005-0114-4502", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad724c37fc354c209b21b9b60431bf8e.json"}}, {"family": "H\u00f6gstrand", "given": "Kari", "initials": "K"}, {"family": "Karimi", "given": "Mohsen", "initials": "M"}, {"family": "Walldin", "given": "Gunilla", "initials": "G", "orcid": "0009-0005-6663-6540", "researcher": {"href": "https://publications.scilifelab.se/researcher/24fb888d0212421eaa2353ed6cc31ac7.json"}}, {"family": "Jansson", "given": "Monika", "initials": "M"}, {"family": "Vonlanthen", "given": "Sofie", "initials": "S", "orcid": "0000-0002-6215-7631", "researcher": {"href": "https://publications.scilifelab.se/researcher/376695e4d6f54d1caf6e776bf537864b.json"}}, {"family": "Ljungman", "given": "Per", "initials": "P", "orcid": "0000-0002-8281-3245", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e5e4220ae354a2e99cd69797638a529.json"}}, {"family": "Langemeijer", "given": "Saskia", "initials": "S"}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T", "orcid": "0000-0003-4283-2983", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6f499e339d2444b817a81ab2712b9e5.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E"}, {"family": "Woll", "given": "Petter S", "initials": "PS", "orcid": "0000-0002-2340-2526", "researcher": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68.json"}}, {"family": "Jacobsen", "given": "Sten Eirik W", "initials": "SEW", "orcid": "0000-0002-1362-3659", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fc5e4f49e4330b095c26cd965cc98.json"}}], "type": "journal article", "published": "2024-03-14", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "143", "issue": "11", "pages": "953-966", "issn-l": "0006-4971"}, "abstract": "Relapse after complete remission (CR) remains the main cause of mortality after allogeneic stem cell transplantation for hematological malignancies and, therefore, improved biomarkers for early prediction of relapse remains a critical goal toward development and assessment of preemptive relapse treatment. Because the significance of cancer stem cells as a source of relapses remains unclear, we investigated whether mutational screening for persistence of rare cancer stem cells would enhance measurable residual disease (MRD) and early relapse prediction after transplantation. In a retrospective study of patients who relapsed and patients who achieved continuous-CR with myelodysplastic syndromes and related myeloid malignancies, combined flow cytometric cell sorting and mutational screening for persistence of rare relapse-initiating stem cells was performed in the bone marrow at multiple CR time points after transplantation. In 25 CR samples from 15 patients that later relapsed, only 9 samples were MRD-positive in mononuclear cells (MNCs) whereas flowcytometric-sorted hematopoietic stem and progenitor cells (HSPCs) were MRD-positive in all samples, and always with a higher variant allele frequency than in MNCs (mean, 97-fold). MRD-positivity in HSPCs preceded MNCs in multiple sequential samples, in some cases preceding relapse by >2 years. In contrast, in 13 patients in long-term continuous-CR, HSPCs remained MRD-negative. Enhanced MRD sensitivity was also observed in total CD34+ cells, but HSPCs were always more clonally involved (mean, 8-fold). In conclusion, identification of relapse-initiating cancer stem cells and mutational MRD screening for their persistence consistently enhances MRD sensitivity and earlier prediction of relapse after allogeneic stem cell transplantation.", "doi": "10.1182/blood.2023022851", "pmid": "38096358", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10950475"}, {"db": "pii", "key": "S0006-4971(23)14644-1"}], "notes": [], "created": "2024-10-21T11:19:06.816Z", "modified": "2024-10-21T11:19:21.211Z"}, {"entity": "publication", "iuid": "b4ff3ca17be540cbb545c1a64ee4e126", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4ff3ca17be540cbb545c1a64ee4e126.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4ff3ca17be540cbb545c1a64ee4e126"}}, "title": "Erythroid Differentiation Enhances RNA Mis-Splicing in SF3B1-Mutant Myelodysplastic Syndromes with Ring Sideroblasts.", "authors": [{"family": "Moura", "given": "Pedro L", "initials": "PL", "orcid": "0000-0002-0493-5394", "researcher": {"href": "https://publications.scilifelab.se/researcher/12216bfd20fa4056b844842908efc829.json"}}, {"family": "Mortera-Blanco", "given": "Teresa", "initials": "T", "orcid": "0000-0002-8399-1430", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a4cccc1f92842b78d19b5c232a655fe.json"}}, {"family": "Hofman", "given": "Isabel J", "initials": "IJ", "orcid": "0000-0001-7825-843X", "researcher": {"href": "https://publications.scilifelab.se/researcher/28b2678b6e1d45299c3a446b4f305762.json"}}, {"family": "Todisco", "given": "Gabriele", "initials": "G", "orcid": "0000-0001-6583-3829", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bdb2b7dcd8a4fa497748ee5e165f11e.json"}}, {"family": "Kretzschmar", "given": "Warren W", "initials": "WW", "orcid": "0000-0002-2575-0807", "researcher": {"href": "https://publications.scilifelab.se/researcher/a67389ef276a47cfacec7cbe50da37a7.json"}}, {"family": "Bj\u00f6rklund", "given": "Ann-Charlotte", "initials": "AC", "orcid": "0009-0008-3745-503X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a03cc050a5d446ca3872007f15db3d3.json"}}, {"family": "Creignou", "given": "Maria", "initials": "M", "orcid": "0000-0002-7629-0871", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7d3e87602e943a296e10038400ff2dc.json"}}, {"family": "Hagemann-Jensen", "given": "Michael", "initials": "M", "orcid": "0000-0002-6423-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/26cb45960bd042c498f4914a342312a0.json"}}, {"family": "Ziegenhain", "given": "Christoph", "initials": "C", "orcid": "0000-0003-2208-4877", "researcher": {"href": "https://publications.scilifelab.se/researcher/3297f21f1a174cd388ac586eda2b5177.json"}}, {"family": "Cabrerizo Granados", "given": "David", "initials": "D", "orcid": "0000-0001-5719-7287", "researcher": {"href": "https://publications.scilifelab.se/researcher/610eac412b5a4527b11776794607930f.json"}}, {"family": "Barbosa", "given": "Indira", "initials": "I", "orcid": "0009-0004-1171-2932", "researcher": {"href": "https://publications.scilifelab.se/researcher/20efd8770db84811a240a8bb70c43939.json"}}, {"family": "Walldin", "given": "Gunilla", "initials": "G", "orcid": "0009-0005-6663-6540", "researcher": {"href": "https://publications.scilifelab.se/researcher/24fb888d0212421eaa2353ed6cc31ac7.json"}}, {"family": "Jansson", "given": "Monika", "initials": "M", "orcid": "0000-0002-9257-0873", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccbf1b2b281742feba0dbd215b6f3228.json"}}, {"family": "Ashley", "given": "Neil", "initials": "N", "orcid": "0000-0002-1655-5137", "researcher": {"href": "https://publications.scilifelab.se/researcher/db3c5c75f5684026a6e267a664c8da99.json"}}, {"family": "Mead", "given": "Adam J", "initials": "AJ", "orcid": "0000-0001-8522-1002", "researcher": {"href": "https://publications.scilifelab.se/researcher/8409c8c7eb604ece9e2ea80ee419336a.json"}}, {"family": "Lundin", "given": "Vanessa", "initials": "V", "orcid": "0000-0003-2335-3370", "researcher": {"href": "https://publications.scilifelab.se/researcher/4648601ee2b74061aadb746516203707.json"}}, {"family": "Dimitriou", "given": "Marios", "initials": "M", "orcid": "0000-0001-8362-2099", "researcher": {"href": "https://publications.scilifelab.se/researcher/531c153359bb400fb48c7324a3bd69ad.json"}}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T", "orcid": "0000-0003-4283-2983", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6f499e339d2444b817a81ab2712b9e5.json"}}, {"family": "Woll", "given": "Petter S", "initials": "PS", "orcid": "0000-0002-2340-2526", "researcher": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68.json"}}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}, {"family": "Sandberg", "given": "Rickard", "initials": "R", "orcid": "0000-0001-6473-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/048c7c9b9edb4366bac7873daad461cd.json"}}, {"family": "Jacobsen", "given": "Sten Eirik W", "initials": "SEW", "orcid": "0000-0002-1362-3659", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fc5e4f49e4330b095c26cd965cc98.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-7839-3743", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bf8d52e24234fa8b348ad08f58d1d48.json"}}], "type": "journal article", "published": "2024-01-16", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "84", "issue": "2", "pages": "211-225", "issn-l": "0008-5472"}, "abstract": "Myelodysplastic syndromes with ring sideroblasts (MDS-RS) commonly develop from hematopoietic stem cells (HSC) bearing mutations in the splicing factor SF3B1 (SF3B1mt). Direct studies into MDS-RS pathobiology have been limited by a lack of model systems that fully recapitulate erythroid biology and RS development and the inability to isolate viable human RS. Here, we combined successful direct RS isolation from patient samples, high-throughput multiomics analysis of cells encompassing the SF3B1mt stem-erythroid continuum, and functional assays to investigate the impact of SF3B1mt on erythropoiesis and RS accumulation. The isolated RS differentiated, egressed into the blood, escaped traditional nonsense-mediated decay (NMD) mechanisms, and leveraged stress-survival pathways that hinder wild-type hematopoiesis through pathogenic GDF15 overexpression. Importantly, RS constituted a contaminant of magnetically enriched CD34+ cells, skewing bulk transcriptomic data. Mis-splicing in SF3B1mt cells was intensified by erythroid differentiation through accelerated RNA splicing and decreased NMD activity, and SF3B1mt led to truncations in several MDS-implicated genes. Finally, RNA mis-splicing induced an uncoupling of RNA and protein expression, leading to critical abnormalities in proapoptotic p53 pathway genes. Overall, this characterization of erythropoiesis in SF3B1mt RS provides a resource for studying MDS-RS and uncovers insights into the unexpectedly active biology of the \"dead-end\" RS.\n\nRing sideroblast isolation combined with state-of-the-art multiomics identifies survival mechanisms underlying SF3B1-mutant erythropoiesis and establishes an active role for erythroid differentiation and ring sideroblasts themselves in SF3B1-mutant myelodysplastic syndrome pathogenesis.", "doi": "10.1158/0008-5472.CAN-23-3038", "pmid": "37921711", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10790130"}, {"db": "pii", "key": "730004"}], "notes": [], "created": "2024-03-14T11:43:21.354Z", "modified": "2025-02-28T14:21:18.908Z"}, {"entity": "publication", "iuid": "758ed2f2baf84c95a00b6eeab7da6edc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/758ed2f2baf84c95a00b6eeab7da6edc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/758ed2f2baf84c95a00b6eeab7da6edc"}}, "title": "Integrated Genomic and Transcriptomic Analysis Improves Disease Classification and Risk Stratification of MDS with Ring Sideroblasts.", "authors": [{"family": "Todisco", "given": "Gabriele", "initials": "G", "orcid": "0000-0001-6583-3829", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bdb2b7dcd8a4fa497748ee5e165f11e.json"}}, {"family": "Creignou", "given": "Maria", "initials": "M", "orcid": "0000-0002-7629-0871", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7d3e87602e943a296e10038400ff2dc.json"}}, {"family": "Bernard", "given": "Elsa", "initials": "E", "orcid": "0000-0002-2057-7187", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a8cab2a7d6b4f17893dddaee1638fb4.json"}}, {"family": "Bj\u00f6rklund", "given": "Ann-Charlotte", "initials": "A"}, {"family": "Moura", "given": "Pedro Luis", "initials": "PL", "orcid": "0000-0002-0493-5394", "researcher": {"href": "https://publications.scilifelab.se/researcher/12216bfd20fa4056b844842908efc829.json"}}, {"family": "Tesi", "given": "Bianca", "initials": "B", "orcid": "0000-0002-8253-2507", "researcher": {"href": "https://publications.scilifelab.se/researcher/96a994cd257c4833a4efe79e26b900ff.json"}}, {"family": "Mortera-Blanco", "given": "Teresa", "initials": "T", "orcid": "0000-0002-8399-1430", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a4cccc1f92842b78d19b5c232a655fe.json"}}, {"family": "Sander", "given": "Birgitta", "initials": "B", "orcid": "0000-0002-1214-1340", "researcher": {"href": "https://publications.scilifelab.se/researcher/f77db1f8ad314f2a84d83a114161080c.json"}}, {"family": "Jansson", "given": "Monika", "initials": "M", "orcid": "0000-0002-9257-0873", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccbf1b2b281742feba0dbd215b6f3228.json"}}, {"family": "Walldin", "given": "Gunilla", "initials": "G", "orcid": "0009-0005-6663-6540", "researcher": {"href": "https://publications.scilifelab.se/researcher/24fb888d0212421eaa2353ed6cc31ac7.json"}}, {"family": "Barbosa", "given": "Indira", "initials": "I", "orcid": "0009-0004-1171-2932", "researcher": {"href": "https://publications.scilifelab.se/researcher/20efd8770db84811a240a8bb70c43939.json"}}, {"family": "Reinsbach", "given": "Susanne E", "initials": "SE", "orcid": "0000-0003-0509-2488", "researcher": {"href": "https://publications.scilifelab.se/researcher/a19438fc9f1a4f6ea1e72f9532dffd80.json"}}, {"family": "Hofman", "given": "Isabel Juliana", "initials": "IJ", "orcid": "0000-0001-7825-843X", "researcher": {"href": "https://publications.scilifelab.se/researcher/28b2678b6e1d45299c3a446b4f305762.json"}}, {"family": "Nilsson", "given": "Christer", "initials": "C", "orcid": "0000-0003-0695-0050", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f78180b33fa48cd86474d5c3cdaa852.json"}}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T", "orcid": "0000-0003-4283-2983", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6f499e339d2444b817a81ab2712b9e5.json"}}, {"family": "Dimitriou", "given": "Marios", "initials": "M", "orcid": "0000-0001-8362-2099", "researcher": {"href": "https://publications.scilifelab.se/researcher/531c153359bb400fb48c7324a3bd69ad.json"}}, {"family": "Chang", "given": "David", "initials": "D", "orcid": "0009-0005-2568-8467", "researcher": {"href": "https://publications.scilifelab.se/researcher/5eb57cd074fa415896ab899308c3b900.json"}}, {"family": "Olafsdottir", "given": "Svannildur", "initials": "S", "orcid": "0009-0002-6357-7029", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c3191617de34dedb33c2514287aec37.json"}}, {"family": "Venckute Larsson", "given": "Sigita", "initials": "S", "orcid": "0009-0005-6187-0231", "researcher": {"href": "https://publications.scilifelab.se/researcher/080916982001432ab671d025ebb0cddc.json"}}, {"family": "Tobiasson", "given": "Magnus", "initials": "M", "orcid": "0000-0002-3633-5852", "researcher": {"href": "https://publications.scilifelab.se/researcher/37b88e8e02af4145b95cc379c68ebee9.json"}}, {"family": "Malcovati", "given": "Luca", "initials": "L", "orcid": "0000-0002-1460-1611", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac37858898774ff29209add33a79fd48.json"}}, {"family": "Woll", "given": "Petter", "initials": "P", "orcid": "0000-0002-2340-2526", "researcher": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68.json"}}, {"family": "Jacobsen", "given": "Sten Eirik W", "initials": "SEW", "orcid": "0000-0002-1362-3659", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fc5e4f49e4330b095c26cd965cc98.json"}}, {"family": "Papaemmanuil", "given": "Elli", "initials": "E", "orcid": "0000-0003-1709-8983", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f67e7f1297e472c8f31639c02d28905.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-7839-3743", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bf8d52e24234fa8b348ad08f58d1d48.json"}}], "type": "journal article", "published": "2023-10-13", "journal": {"title": "Clin. Cancer Res.", "issn": "1557-3265", "issn-l": "1078-0432", "volume": "29", "issue": "20", "pages": "4256-4267"}, "abstract": "Ring sideroblasts (RS) define the low-risk myelodysplastic neoplasm (MDS) subgroup with RS but may also reflect erythroid dysplasia in higher risk myeloid neoplasm. The benign behavior of MDS with RS (MDSRS+) is limited to SF3B1-mutated cases without additional high-risk genetic events, but one third of MDSRS+ carry no SF3B1 mutation, suggesting that different molecular mechanisms may underlie RS formation. We integrated genomic and transcriptomic analyses to evaluate whether transcriptome profiles may improve current risk stratification.\r\n\r\nWe studied a prospective cohort of MDSRS+ patients irrespective of World Health Organization (WHO) class with regard to somatic mutations, copy-number alterations, and bone marrow CD34+ cell transcriptomes to assess whether transcriptome profiles add to prognostication and provide input on disease classification.\r\n\r\nSF3B1, SRSF2, or TP53 multihit mutations were found in 89% of MDSRS+ cases, and each mutation category was associated with distinct clinical outcome, gene expression, and alternative splicing profiles. Unsupervised clustering analysis identified three clusters with distinct hemopoietic stem and progenitor (HSPC) composition, which only partially overlapped with mutation groups. IPSS-M and the transcriptome-defined proportion of megakaryocyte/erythroid progenitors (MEP) independently predicted survival in multivariable analysis.\r\n\r\nThese results provide essential input on the molecular basis of SF3B1-unmutated MDSRS+ and propose HSPC quantification as a prognostic marker in myeloid neoplasms with RS.", "doi": "10.1158/1078-0432.CCR-23-0538", "pmid": "37498312", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10570683"}, {"db": "pii", "key": "728030"}], "notes": [], "created": "2023-11-22T11:16:24.579Z", "modified": "2025-11-28T19:52:07.783Z"}, {"entity": "publication", "iuid": "b6fc0f9d7a044833846df2ea3ca6b15b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b6fc0f9d7a044833846df2ea3ca6b15b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b6fc0f9d7a044833846df2ea3ca6b15b"}}, "title": "A T cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo.", "authors": [{"family": "Giannakopoulou", "given": "Eirini", "initials": "E"}, {"family": "Lehander", "given": "Madeleine", "initials": "M"}, {"family": "Virding Culleton", "given": "Stina", "initials": "S"}, {"family": "Yang", "given": "Weiwen", "initials": "W"}, {"family": "Li", "given": "Yingqian", "initials": "Y"}, {"family": "Karpanen", "given": "Terhi", "initials": "T", "orcid": "0000-0002-2803-083X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca6013dbea3045e798ce756d45b9777f.json"}}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T"}, {"family": "Rustad", "given": "Even H", "initials": "EH"}, {"family": "Nielsen", "given": "Morten Milek", "initials": "MM"}, {"family": "Bollineni", "given": "Ravi Chand", "initials": "RC"}, {"family": "Tran", "given": "Trung T", "initials": "TT"}, {"family": "Delic-Sarac", "given": "Marina", "initials": "M"}, {"family": "Gjerdingen", "given": "Thea Johanne", "initials": "TJ"}, {"family": "Douvlataniotis", "given": "Karolos", "initials": "K"}, {"family": "Laos", "given": "Maarja", "initials": "M"}, {"family": "Ali", "given": "Muhammad", "initials": "M"}, {"family": "Hillen", "given": "Amy", "initials": "A", "orcid": "0000-0002-8567-1545", "researcher": {"href": "https://publications.scilifelab.se/researcher/fba7f6c5a2f04d71816a8381ede8a615.json"}}, {"family": "Mazzi", "given": "Stefania", "initials": "S"}, {"family": "Chin", "given": "Desmond Wai Loon", "initials": "DWL"}, {"family": "Mehta", "given": "Adi", "initials": "A"}, {"family": "Holm", "given": "Jeppe Sejer\u00f8", "initials": "JS"}, {"family": "Bentzen", "given": "Amalie Kai", "initials": "AK"}, {"family": "Bill", "given": "Marie", "initials": "M"}, {"family": "Griffioen", "given": "Marieke", "initials": "M", "orcid": "0000-0002-3001-4441", "researcher": {"href": "https://publications.scilifelab.se/researcher/1cb97023cdb84dd0aaecc659eca5d6a3.json"}}, {"family": "Gedde-Dahl", "given": "Tobias", "initials": "T"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}, {"family": "Jacobsen", "given": "Sten Eirik W", "initials": "SEW", "orcid": "0000-0002-1362-3659", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fc5e4f49e4330b095c26cd965cc98.json"}}, {"family": "Woll", "given": "Petter S", "initials": "PS", "orcid": "0000-0002-2340-2526", "researcher": {"href": "https://publications.scilifelab.se/researcher/77ae0c1d2cf5461894c6d0d80ed42f68.json"}}, {"family": "Olweus", "given": "Johanna", "initials": "J", "orcid": "0000-0002-1898-3100", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bbcafcada6a4586948b50153464ec60.json"}}], "type": "journal article", "published": "2023-10-02", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "issn-l": null}, "abstract": "Acute myeloid leukemia (AML), the most frequent leukemia in adults, is driven by recurrent somatically acquired genetic lesions in a restricted number of genes. Treatment with tyrosine kinase inhibitors has demonstrated that targeting of prevalent FMS-related receptor tyrosine kinase 3 (FLT3) gain-of-function mutations can provide significant survival benefits for patients, although the efficacy of FLT3 inhibitors in eliminating FLT3-mutated clones is variable. We identified a T cell receptor (TCR) reactive to the recurrent D835Y driver mutation in the FLT3 tyrosine kinase domain (TCRFLT3D/Y). TCRFLT3D/Y-redirected T cells selectively eliminated primary human AML cells harboring the FLT3D835Y mutation in vitro and in vivo. TCRFLT3D/Y cells rejected both CD34+ and CD34- AML in mice engrafted with primary leukemia from patients, reaching minimal residual disease-negative levels, and eliminated primary CD34+ AML leukemia-propagating cells in vivo. Thus, T cells targeting a single shared mutation can provide efficient immunotherapy toward selective elimination of clonally involved primary AML cells in vivo.", "doi": "10.1038/s43018-023-00642-8", "pmid": "37783807", "labels": {"NGI Short read": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s43018-023-00642-8"}], "notes": [], "created": "2023-10-19T13:55:47.476Z", "modified": "2023-10-19T13:55:47.704Z"}]}