{"entity": "researcher", "timestamp": "2026-06-12T13:50:40.998Z", "family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "affiliations": ["Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan;"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d"}}, "publications": [{"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": "d9be4ec5baae47499d9976f9b113a4d0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d9be4ec5baae47499d9976f9b113a4d0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d9be4ec5baae47499d9976f9b113a4d0"}}, "title": "Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.", "authors": [{"family": "Butler-Laporte", "given": "Guillaume", "initials": "G", "orcid": "0000-0001-5388-0396", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c165ac40c3c409b93acbb13ac63579a.json"}}, {"family": "Povysil", "given": "Gundula", "initials": "G", "orcid": "0000-0003-4625-5909", "researcher": {"href": "https://publications.scilifelab.se/researcher/78129fef5aad4ba8ad154d9a4908974f.json"}}, {"family": "Kosmicki", "given": "Jack A", "initials": "JA", "orcid": "0000-0003-1252-6192", "researcher": {"href": "https://publications.scilifelab.se/researcher/21b8896b49bd48a6b9b21b84a76cda41.json"}}, {"family": "Cirulli", "given": "Elizabeth T", "initials": "ET", "orcid": "0000-0001-7808-2809", "researcher": {"href": "https://publications.scilifelab.se/researcher/566755e2fb34412c93b01245e512f9fd.json"}}, {"family": "Drivas", "given": "Theodore", "initials": "T", "orcid": "0000-0002-8717-0111", "researcher": {"href": "https://publications.scilifelab.se/researcher/0adcb730c0f644ceb712e774801cb74a.json"}}, {"family": "Furini", "given": "Simone", "initials": "S"}, {"family": "Saad", "given": "Chadi", "initials": "C", "orcid": "0000-0001-6963-9126", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac0b588b98a7496aa8a422ce08dd89c9.json"}}, {"family": "Schmidt", "given": "Axel", "initials": "A", "orcid": "0000-0002-1185-3012", "researcher": {"href": "https://publications.scilifelab.se/researcher/3708b225fbae4c239bdc3bea34beff17.json"}}, {"family": "Olszewski", "given": "Pawel", "initials": "P", "orcid": "0000-0003-1010-8843", "researcher": {"href": "https://publications.scilifelab.se/researcher/175cf3dd63e54f7c919ed3b1de3d4b11.json"}}, {"family": "Korotko", "given": "Urszula", "initials": "U", "orcid": "0000-0002-1779-8368", "researcher": {"href": "https://publications.scilifelab.se/researcher/9960078bdffa4561a9111e37390c44eb.json"}}, {"family": "Quinodoz", "given": "Mathieu", "initials": "M", "orcid": "0000-0002-9841-4433", "researcher": {"href": "https://publications.scilifelab.se/researcher/140e63b09c3340a0ae6aeb8124ea15b1.json"}}, {"family": "\u00c7elik", "given": "Elifnaz", "initials": "E", "orcid": "0000-0002-0324-5228", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a15c971dbe44bda2ee9381196c6f23.json"}}, {"family": "Kundu", "given": "Kousik", "initials": "K", "orcid": "0000-0002-1019-8351", "researcher": {"href": "https://publications.scilifelab.se/researcher/55dbffb9b2234f8db2b17025bd053aa7.json"}}, {"family": "Walter", "given": "Klaudia", "initials": "K", "orcid": "0000-0003-4448-0301", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd5029beabb34e18869a535f9578bbd6.json"}}, {"family": "Jung", "given": "Junghyun", "initials": "J"}, {"family": "Stockwell", "given": "Amy D", "initials": "AD"}, {"family": "Sloofman", "given": "Laura G", "initials": "LG", "orcid": "0000-0001-7628-4378", "researcher": {"href": "https://publications.scilifelab.se/researcher/03b834030a6e4aef8e9340a0a8bab91d.json"}}, {"family": "Jordan", "given": "Daniel M", "initials": "DM", "orcid": "0000-0002-5318-8225", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5123b5265ee4ba5ab7e23ffaa9177ca.json"}}, {"family": "Thompson", "given": "Ryan C", "initials": "RC", "orcid": "0000-0002-0450-8181", "researcher": {"href": "https://publications.scilifelab.se/researcher/18e5041ace5249e9b5eda7ffd7e8fdbb.json"}}, {"family": "Del Valle", "given": "Diane", "initials": "D", "orcid": "0000-0001-6983-5362", "researcher": {"href": "https://publications.scilifelab.se/researcher/e63491ffb2b34e40b038c46206561813.json"}}, {"family": "Simons", "given": "Nicole", "initials": "N", "orcid": "0000-0002-3952-1458", "researcher": {"href": "https://publications.scilifelab.se/researcher/989038ff4ca94453a1c53435a13b0936.json"}}, {"family": "Cheng", "given": "Esther", "initials": "E"}, {"family": "Sebra", "given": "Robert", "initials": "R"}, {"family": "Schadt", "given": "Eric E", "initials": "EE"}, {"family": "Kim-Schulze", "given": "Seunghee", "initials": "S"}, {"family": "Gnjatic", "given": "Sacha", "initials": "S"}, {"family": "Merad", "given": "Miriam", "initials": "M"}, {"family": "Buxbaum", "given": "Joseph D", "initials": "JD"}, {"family": "Beckmann", "given": "Noam D", "initials": "ND"}, {"family": "Charney", "given": "Alexander W", "initials": "AW"}, {"family": "Przychodzen", "given": "Bartlomiej", "initials": "B"}, {"family": "Chang", "given": "Timothy", "initials": "T", "orcid": "0000-0002-9225-9874", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a8e6da514524249bf7f659e6ac0fd37.json"}}, {"family": "Pottinger", "given": "Tess D", "initials": "TD"}, {"family": "Shang", "given": "Ning", "initials": "N"}, {"family": "Brand", "given": "Fabian", "initials": "F", "orcid": "0000-0003-1885-7021", "researcher": {"href": "https://publications.scilifelab.se/researcher/deeffbb73a484059b233f655a7ec9b2a.json"}}, {"family": "Fava", "given": "Francesca", "initials": "F"}, {"family": "Mari", "given": "Francesca", "initials": "F"}, {"family": "Chwialkowska", "given": "Karolina", "initials": "K", "orcid": "0000-0001-8053-8959", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f2e48406c854c07b36fdfd389669dca.json"}}, {"family": "Niemira", "given": "Magdalena", "initials": "M", "orcid": "0000-0002-0701-4961", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a5a941aefa1415da58a2e2c06a61475.json"}}, {"family": "Pula", "given": "Szymon", "initials": "S", "orcid": "0000-0002-5684-5358", "researcher": {"href": "https://publications.scilifelab.se/researcher/bee449a4cb304996919dc8bc4ef3cef3.json"}}, {"family": "Baillie", "given": "J Kenneth", "initials": "JK"}, {"family": "Stuckey", "given": "Alex", "initials": "A", "orcid": "0000-0001-8636-737X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e613c25c28c44551a51c6f5029ce429f.json"}}, {"family": "Salas", "given": "Antonio", "initials": "A"}, {"family": "Bello", "given": "Xabier", "initials": "X", "orcid": "0000-0002-4990-8496", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f6c5c66e6dc4bd9b17ea8f99dcdb1c3.json"}}, {"family": "Pardo-Seco", "given": "Jacobo", "initials": "J"}, {"family": "G\u00f3mez-Carballa", "given": "Alberto", "initials": "A"}, {"family": "Rivero-Calle", "given": "Irene", "initials": "I"}, {"family": "Martin\u00f3n-Torres", "given": "Federico", "initials": "F"}, {"family": "Ganna", "given": "Andrea", "initials": "A"}, {"family": "Karczewski", "given": "Konrad J", "initials": "KJ", "orcid": "0000-0003-2878-4671", "researcher": {"href": "https://publications.scilifelab.se/researcher/096bfb156b54478e9a3f9c9d7730bc43.json"}}, {"family": "Veerapen", "given": "Kumar", "initials": "K"}, {"family": "Bourgey", "given": "Mathieu", "initials": "M", "orcid": "0000-0002-8432-834X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7db054c6632438284888857aa54ada4.json"}}, {"family": "Bourque", "given": "Guillaume", "initials": "G", "orcid": "0000-0002-3933-9656", "researcher": {"href": "https://publications.scilifelab.se/researcher/d72fde1b19d2491387b5df6429bb238e.json"}}, {"family": "Eveleigh", "given": "Robert Jm", "initials": "RJ", "orcid": "0000-0002-4147-382X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4455277bbf4f47df96377ca92c2e2c5d.json"}}, {"family": "Forgetta", "given": "Vincenzo", "initials": "V"}, {"family": "Morrison", "given": "David", "initials": "D", "orcid": "0000-0001-8380-3615", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cf4ef09fddb4438af55861445d796ef.json"}}, {"family": "Langlais", "given": "David", "initials": "D", "orcid": "0000-0003-4429-0110", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bc9421a0159458990b6bc1189cbb7fc.json"}}, {"family": "Lathrop", "given": "Mark", "initials": "M"}, {"family": "Mooser", "given": "Vincent", "initials": "V", "orcid": "0000-0002-8632-0448", "researcher": {"href": "https://publications.scilifelab.se/researcher/97298e39568c461d9e174ff74c42e3f8.json"}}, {"family": "Nakanishi", "given": "Tomoko", "initials": "T", "orcid": "0000-0001-9510-5646", "researcher": {"href": "https://publications.scilifelab.se/researcher/156825097e204173b62131f9312b98b1.json"}}, {"family": "Frithiof", "given": "Robert", "initials": "R", "orcid": "0000-0003-2278-7951", "researcher": {"href": "https://publications.scilifelab.se/researcher/8fec11dd18f941b7842610ad14237a35.json"}}, {"family": "Hultstr\u00f6m", "given": "Michael", "initials": "M", "orcid": "0000-0003-4675-1099", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9a74d3380a24c31930e6e671e685b5b.json"}}, {"family": "Lipcsey", "given": "Miklos", "initials": "M", "orcid": "0000-0002-1976-4129", "researcher": {"href": "https://publications.scilifelab.se/researcher/81805f2324634628abefcf0ab6ce6a15.json"}}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Schiabor Barrett", "given": "Kelly M", "initials": "KM", "orcid": "0000-0001-6194-787X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e91dff1c84cb4accb893cbd711df3eb7.json"}}, {"family": "Lee", "given": "William", "initials": "W"}, {"family": "Bolze", "given": "Alexandre", "initials": "A", "orcid": "0000-0001-7399-2766", "researcher": {"href": "https://publications.scilifelab.se/researcher/99d7674f36d44b05b224d486d987521d.json"}}, {"family": "White", "given": "Simon", "initials": "S", "orcid": "0000-0001-6375-2363", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad52dae860c34ec9ab4ec9ebabffac7f.json"}}, {"family": "Riffle", "given": "Stephen", "initials": "S"}, {"family": "Tanudjaja", "given": "Francisco", "initials": "F"}, {"family": "Sandoval", "given": "Efren", "initials": "E"}, {"family": "Neveux", "given": "Iva", "initials": "I"}, {"family": "Dabe", "given": "Shaun", "initials": "S", "orcid": "0000-0002-2494-962X", "researcher": {"href": "https://publications.scilifelab.se/researcher/518051e39cdf4f20b202a8283421d0be.json"}}, {"family": "Casadei", "given": "Nicolas", "initials": "N", "orcid": "0000-0003-2209-0580", "researcher": {"href": 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"orcid": "0000-0001-7627-0259", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e797709a3f9473c851d79ababa3e680.json"}}, {"family": "Kiryluk", "given": "Krzysztof", "initials": "K", "orcid": "0000-0002-5047-6715", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6e7b5668c0141728599d5ebb68c8929.json"}}, {"family": "Renieri", "given": "Alessandra", "initials": "A", "orcid": "0000-0002-0846-9220", "researcher": {"href": "https://publications.scilifelab.se/researcher/3dbf990f1e0c4fd99e45c945915f25b0.json"}}, {"family": "Ferreira", "given": "Manuel A R", "initials": "MAR", "orcid": "0000-0001-9059-1825", "researcher": {"href": "https://publications.scilifelab.se/researcher/d27aef5015494b018b22352125c0225d.json"}}, {"family": "Richards", "given": "J Brent", "initials": "JB", "orcid": "0000-0002-3746-9086", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2c20c901fd041c194dae79b29b94ec2.json"}}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "issn-l": "1553-7390", "volume": "18", "issue": "11", "pages": "e1010367"}, "abstract": "Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.", "doi": "10.1371/journal.pgen.1010367", "pmid": "36327219", "labels": {"NGI Short read": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "National Genomics Infrastructure": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9632827"}, {"db": "pii", "key": "PGENETICS-D-22-00434"}], "notes": [], "created": "2022-11-29T14:02:16.675Z", "modified": "2023-06-16T12:55:14.973Z"}, {"entity": "publication", "iuid": "44c68df58df94563bf7a0681cd336695", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44c68df58df94563bf7a0681cd336695.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44c68df58df94563bf7a0681cd336695"}}, "title": "Co-mutation pattern, clonal hierarchy, and clone size concur to determine disease phenotype of SRSF2P95-mutated neoplasms.", "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"}, {"family": "Gall\u00ec", "given": "Anna", "initials": "A", "orcid": "0000-0002-4039-3756", "researcher": {"href": "https://publications.scilifelab.se/researcher/da521c0c7ebe434f96c80cc5ca3c6e11.json"}}, {"family": "Guglielmelli", "given": "Paola", "initials": "P", "orcid": "0000-0003-1809-284X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b850e020a94344e8afc3aef21b587e41.json"}}, {"family": "Rumi", "given": "Elisa", "initials": "E", "orcid": "0000-0002-7572-9504", "researcher": {"href": "https://publications.scilifelab.se/researcher/c76668503aa74ad48d9ad8267e83d5ab.json"}}, {"family": "Roncador", "given": "Marco", "initials": "M"}, {"family": "Rizzo", "given": "Ettore", "initials": "E"}, {"family": "Nannya", "given": "Yasuhito", "initials": "Y"}, {"family": "Pietra", "given": "Daniela", "initials": "D", "orcid": "0000-0002-6575-8766", "researcher": {"href": "https://publications.scilifelab.se/researcher/e68d2895241a42858ed4251df90b0cbe.json"}}, {"family": "Elena", "given": "Chiara", "initials": "C"}, {"family": "Bono", "given": "Elisa", "initials": "E"}, {"family": "Molteni", "given": "Elisabetta", "initials": "E"}, {"family": "Rosti", "given": "Vittorio", "initials": "V"}, {"family": "Catrical\u00e1", "given": "Silvia", "initials": "S"}, {"family": "Sarchi", "given": "Martina", "initials": "M"}, {"family": "Dimitriou", "given": "Marios", "initials": "M", "orcid": "0000-0001-8362-2099", "researcher": {"href": "https://publications.scilifelab.se/researcher/531c153359bb400fb48c7324a3bd69ad.json"}}, {"family": "Ungerstedt", "given": "Johanna", "initials": "J"}, {"family": "Vannucchi", "given": "Alessandro Maria", "initials": "AM"}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E"}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}, {"family": "Cazzola", "given": "Mario", "initials": "M", "orcid": "0000-0001-6984-8817", "researcher": {"href": "https://publications.scilifelab.se/researcher/e85ab5f89c604aad824a42107184f196.json"}}, {"family": "Malcovati", "given": "Luca", "initials": "L", "orcid": "0000-0002-1460-1611", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac37858898774ff29209add33a79fd48.json"}}], "type": "journal article", "published": "2021-08-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "35", "issue": "8", "pages": "2371-2381", "issn-l": "0887-6924"}, "abstract": "Somatic mutations in splicing factor genes frequently occur in myeloid neoplasms. While SF3B1 mutations are associated with myelodysplastic syndromes (MDS) with ring sideroblasts, SRSF2P95 mutations are found in different disease categories, including MDS, myeloproliferative neoplasms (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), and acute myeloid leukemia (AML). To identify molecular determinants of this phenotypic heterogeneity, we explored molecular and clinical features of a prospective cohort of 279 SRSF2P95-mutated cases selected from a population of 2663 patients with myeloid neoplasms. Median number of somatic mutations per subject was 3. Multivariate regression analysis showed associations between co-mutated genes and clinical phenotype, including JAK2 or MPL with myelofibrosis (OR = 26.9); TET2 with monocytosis (OR = 5.2); RAS-pathway genes with leukocytosis (OR = 5.1); and STAG2, RUNX1, or IDH1/2 with blast phenotype (MDS or AML) (OR = 3.4, 1.9, and 2.1, respectively). Within patients with SRSF2-JAK2 co-mutation, JAK2 dominance was invariably associated with clinical feature of MPN, whereas SRSF2 mutation was dominant in MDS/MPN. Within patients with SRSF2-TET2 co-mutation, clinical expressivity of monocytosis was positively associated with co-mutated clone size. This study provides evidence that co-mutation pattern, clone size, and hierarchy concur to determine clinical phenotype, tracing relevant genotype-phenotype associations across disease entities and giving insight on unaccountable clinical heterogeneity within current WHO classification categories.", "doi": "10.1038/s41375-020-01106-z", "pmid": "33349666", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41375-020-01106-z"}], "notes": [], "created": "2021-12-06T08:28:45.875Z", "modified": "2021-12-06T08:28:46.127Z"}, {"entity": "publication", "iuid": "2c61a438d2924bd587d6cc6f0e3dcefe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c61a438d2924bd587d6cc6f0e3dcefe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c61a438d2924bd587d6cc6f0e3dcefe"}}, "title": "Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes.", "authors": [{"family": "Bernard", "given": "Elsa", "initials": "E", "orcid": "0000-0002-2057-7187", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a8cab2a7d6b4f17893dddaee1638fb4.json"}}, {"family": "Nannya", "given": "Yasuhito", "initials": "Y"}, {"family": "Hasserjian", "given": "Robert P", "initials": "RP"}, {"family": "Devlin", "given": "Sean M", "initials": "SM"}, {"family": "Tuechler", "given": "Heinz", "initials": "H", "orcid": "0000-0002-1568-3436", "researcher": {"href": "https://publications.scilifelab.se/researcher/8aeeedfebec14b7c9af34915b5320432.json"}}, {"family": "Medina-Martinez", "given": "Juan S", "initials": "JS"}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T", "orcid": "0000-0003-4283-2983", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6f499e339d2444b817a81ab2712b9e5.json"}}, {"family": "Shiozawa", "given": "Yusuke", "initials": "Y"}, {"family": "Saiki", "given": "Ryunosuke", "initials": "R"}, {"family": "Malcovati", "given": "Luca", "initials": "L"}, {"family": "Levine", "given": "Max F", "initials": "MF", "orcid": "0000-0001-5156-9086", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a65c2d5e4ea4c7fa4823821a995b0ec.json"}}, {"family": "Arango", "given": "Juan E", "initials": "JE"}, {"family": "Zhou", "given": "Yangyu", "initials": "Y"}, {"family": "Sol\u00e9", "given": "Francesc", "initials": "F"}, {"family": "Cargo", "given": "Catherine A", "initials": "CA"}, {"family": "Haase", "given": "Detlef", "initials": "D"}, {"family": "Creignou", "given": "Maria", "initials": "M"}, {"family": "Germing", "given": "Ulrich", "initials": "U"}, {"family": "Zhang", "given": "Yanming", "initials": "Y"}, {"family": "Gundem", "given": "Gunes", "initials": "G"}, {"family": "Sarian", "given": "Araxe", "initials": "A"}, {"family": "van de Loosdrecht", "given": "Arjan A", "initials": "AA"}, {"family": "J\u00e4dersten", "given": "Martin", "initials": "M"}, {"family": "Tobiasson", "given": "Magnus", "initials": "M"}, {"family": "Kosmider", "given": "Olivier", "initials": "O"}, {"family": "Follo", "given": "Matilde Y", "initials": "MY", "orcid": "0000-0001-6126-0859", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cbe3a0c22f7454b87bcfa2737a9a2cc.json"}}, {"family": "Thol", "given": "Felicitas", "initials": "F"}, {"family": "Pinheiro", "given": "Ronald F", "initials": "RF"}, {"family": "Santini", "given": "Valeria", "initials": "V"}, {"family": "Kotsianidis", "given": "Ioannis", "initials": "I"}, {"family": "Boultwood", "given": "Jacqueline", "initials": "J", "orcid": "0000-0002-4330-2928", "researcher": {"href": "https://publications.scilifelab.se/researcher/389b184fad7048daaa8bd0466b298374.json"}}, {"family": "Santos", "given": "Fabio P S", "initials": "FPS"}, {"family": "Schanz", "given": "Julie", "initials": "J"}, {"family": "Kasahara", "given": "Senji", "initials": "S"}, {"family": "Ishikawa", "given": "Takayuki", "initials": "T"}, {"family": "Tsurumi", "given": "Hisashi", "initials": "H"}, {"family": "Takaori-Kondo", "given": "Akifumi", "initials": "A", "orcid": "0000-0001-7678-4284", "researcher": {"href": "https://publications.scilifelab.se/researcher/580e4d306fca4abeb09cea24b9fb381e.json"}}, {"family": "Kiguchi", "given": "Toru", "initials": "T"}, {"family": "Polprasert", "given": "Chantana", "initials": "C"}, {"family": "Bennett", "given": "John M", "initials": "JM"}, {"family": "Klimek", "given": "Virginia M", "initials": "VM"}, {"family": "Savona", "given": "Michael R", "initials": "MR", "orcid": "0000-0003-3763-5504", "researcher": {"href": "https://publications.scilifelab.se/researcher/50a3df7d0cee4ad484ba249dc87de866.json"}}, {"family": "Belickova", "given": "Monika", "initials": "M", "orcid": "0000-0002-9158-881X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ff36ac18c71412b94d17252c44e70bd.json"}}, {"family": "Ganster", "given": "Christina", "initials": "C", "orcid": "0000-0002-7566-5985", "researcher": {"href": "https://publications.scilifelab.se/researcher/572629d9ced648fab310107d492fec38.json"}}, {"family": "Palomo", "given": "Laura", "initials": "L"}, {"family": "Sanz", "given": "Guillermo", "initials": "G", "orcid": "0000-0002-2767-8191", "researcher": {"href": "https://publications.scilifelab.se/researcher/df83862e8b6d43d7ae2707e28420218f.json"}}, {"family": "Ades", "given": "Lionel", "initials": "L"}, {"family": "Della Porta", "given": "Matteo Giovanni", "initials": "MG"}, {"family": "Elias", "given": "Harold K", "initials": "HK"}, {"family": "Smith", "given": "Alexandra G", "initials": "AG"}, {"family": "Werner", "given": "Yesenia", "initials": "Y"}, {"family": "Patel", "given": "Minal", "initials": "M"}, {"family": "Viale", "given": "Agn\u00e8s", "initials": "A"}, {"family": "Vanness", "given": "Katelynd", "initials": "K"}, {"family": "Neuberg", "given": "Donna S", "initials": "DS", "orcid": "0000-0003-2566-3145", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2f9cbb622f040bebdfcb68657035be1.json"}}, {"family": "Stevenson", "given": "Kristen E", "initials": "KE"}, {"family": "Menghrajani", "given": "Kamal", "initials": "K"}, {"family": "Bolton", "given": "Kelly L", "initials": "KL"}, {"family": "Fenaux", "given": "Pierre", "initials": "P"}, {"family": "Pellagatti", "given": "Andrea", "initials": "A"}, {"family": "Platzbecker", "given": "Uwe", "initials": "U"}, {"family": "Heuser", "given": "Michael", "initials": "M", "orcid": "0000-0001-5318-9044", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb00432d76f74293a5acdbc17a3f2305.json"}}, {"family": "Valent", "given": "Peter", "initials": "P"}, {"family": "Chiba", "given": "Shigeru", "initials": "S"}, {"family": "Miyazaki", "given": "Yasushi", "initials": "Y"}, {"family": "Finelli", "given": "Carlo", "initials": "C"}, {"family": "Voso", "given": "Maria Teresa", "initials": "MT", "orcid": "0000-0002-6164-4761", "researcher": {"href": "https://publications.scilifelab.se/researcher/54c19342a17e44249d7b4e4ae05d3e7a.json"}}, {"family": "Shih", "given": "Lee-Yung", "initials": "LY"}, {"family": "Fontenay", "given": "Michaela", "initials": "M", "orcid": "0000-0002-5492-6349", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a304a24a07e4f66b50eb9b3204d7eb4.json"}}, {"family": "Jansen", "given": "Joop H", "initials": "JH"}, {"family": "Cervera", "given": "Jos\u00e9", "initials": "J"}, {"family": "Atsuta", "given": "Yoshiko", "initials": "Y"}, {"family": "Gattermann", "given": "Norbert", "initials": "N"}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL", "orcid": "0000-0003-0197-5451", "researcher": {"href": "https://publications.scilifelab.se/researcher/eeb0be1eb2be4bb48ec7f9dc17bd696f.json"}}, {"family": "Bejar", "given": "Rafael", "initials": "R", "orcid": "0000-0002-5603-4598", "researcher": {"href": "https://publications.scilifelab.se/researcher/33fcd878bc6e48e98950a35a0cebdbbb.json"}}, {"family": "Greenberg", "given": "Peter L", "initials": "PL"}, {"family": "Cazzola", "given": "Mario", "initials": "M", "orcid": "0000-0001-6984-8817", "researcher": {"href": "https://publications.scilifelab.se/researcher/e85ab5f89c604aad824a42107184f196.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E"}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}, {"family": "Papaemmanuil", "given": "Elli", "initials": "E", "orcid": "0000-0003-1709-8983", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f67e7f1297e472c8f31639c02d28905.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "volume": "26", "issue": "10", "pages": "1549-1556", "issn-l": "1078-8956"}, "abstract": "Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6-8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response.", "doi": "10.1038/s41591-020-1008-z", "pmid": "32747829", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-020-1008-z"}, {"db": "pmc", "key": "PMC8381722"}, {"db": "mid", "key": "NIHMS1715889"}], "notes": [], "created": "2020-12-10T14:46:50.666Z", "modified": "2021-11-10T12:46:47.582Z"}, {"entity": "publication", "iuid": "d7e8b72bb7424ac1a101bd09cdf9cc30", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d7e8b72bb7424ac1a101bd09cdf9cc30.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d7e8b72bb7424ac1a101bd09cdf9cc30"}}, "title": "SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS.", "authors": [{"family": "Malcovati", "given": "Luca", "initials": "L"}, {"family": "Stevenson", "given": "Kristen", "initials": "K"}, {"family": "Papaemmanuil", "given": "Elli", "initials": "E"}, {"family": "Neuberg", "given": "Donna", "initials": "D"}, {"family": "Bejar", "given": "Rafael", "initials": "R", "orcid": "0000-0002-5603-4598", "researcher": {"href": "https://publications.scilifelab.se/researcher/33fcd878bc6e48e98950a35a0cebdbbb.json"}}, {"family": "Boultwood", "given": "Jacqueline", "initials": "J", "orcid": "0000-0002-4330-2928", "researcher": {"href": "https://publications.scilifelab.se/researcher/389b184fad7048daaa8bd0466b298374.json"}}, {"family": "Bowen", "given": "David T", "initials": "DT"}, {"family": "Campbell", "given": "Peter J", "initials": "PJ"}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL"}, {"family": "Fenaux", "given": "Pierre", "initials": "P"}, {"family": "Haferlach", "given": "Torsten", "initials": "T"}, {"family": "Heuser", "given": "Michael", "initials": "M"}, {"family": "Jansen", "given": "Joop H", "initials": "JH"}, {"family": "Komrokji", "given": "Rami S", "initials": "RS"}, {"family": "Maciejewski", "given": "Jaroslaw P", "initials": "JP"}, {"family": "Walter", "given": "Matthew J", "initials": "MJ"}, {"family": "Fontenay", "given": "Michaela", "initials": "M"}, {"family": "Garcia-Manero", "given": "Guillermo", "initials": "G"}, {"family": "Graubert", "given": "Timothy A", "initials": "TA"}, {"family": "Karsan", "given": "Aly", "initials": "A"}, {"family": "Meggendorfer", "given": "Manja", "initials": "M"}, {"family": "Pellagatti", "given": "Andrea", "initials": "A"}, {"family": "Sallman", "given": "David A", "initials": "DA"}, {"family": "Savona", "given": "Michael R", "initials": "MR", "orcid": "0000-0003-3763-5504", "researcher": {"href": "https://publications.scilifelab.se/researcher/50a3df7d0cee4ad484ba249dc87de866.json"}}, {"family": "Sekeres", "given": "Mikkael A", "initials": "MA"}, {"family": "Steensma", "given": "David P", "initials": "DP", "orcid": "0000-0001-5130-9284", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dbccbde21fc4819b45583d5ecefc3e6.json"}}, {"family": "Tauro", "given": "Sudhir", "initials": "S", "orcid": "0000-0002-7236-970X", "researcher": {"href": "https://publications.scilifelab.se/researcher/311f863e8ab747468fafc068f4d1d297.json"}}, {"family": "Thol", "given": "Felicitas", "initials": "F"}, {"family": "Vyas", "given": "Paresh", "initials": "P", "orcid": "0000-0003-3931-0914", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbe356d5bf3e4965a2e82c4c0bb32ed8.json"}}, {"family": "Van de Loosdrecht", "given": "Arjan A", "initials": "AA"}, {"family": "Haase", "given": "Detlef", "initials": "D"}, {"family": "T\u00fcchler", "given": "Heinz", "initials": "H"}, {"family": "Greenberg", "given": "Peter L", "initials": "PL"}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}, {"family": "Hellstrom-Lindberg", "given": "Eva", "initials": "E"}, {"family": "Cazzola", "given": "Mario", "initials": "M"}], "type": "journal article", "published": "2020-07-09", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "136", "issue": "2", "pages": "157-170", "issn-l": "0006-4971"}, "abstract": "The 2016 revision of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. Approximately half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. SF3B1 mutation identifies a condition characterized by ring sideroblasts (RS), ineffective erythropoiesis, and indolent clinical course. A large body of evidence supports recognition of SF3B1-mutant MDS as a distinct nosologic entity. To further validate this notion, we interrogated the data set of the International Working Group for the Prognosis of MDS (IWG-PM). Based on the findings of our analyses, we propose the following diagnostic criteria for SF3B1-mutant MDS: (1) cytopenia as defined by standard hematologic values, (2) somatic SF3B1 mutation, (3) morphologic dysplasia (with or without RS), and (4) bone marrow blasts <5% and peripheral blood blasts <1%. Selected concomitant genetic lesions represent exclusion criteria for the proposed entity. In patients with clonal cytopenia of undetermined significance, SF3B1 mutation is almost invariably associated with subsequent development of overt MDS with RS, suggesting that this genetic lesion might provide presumptive evidence of MDS in the setting of persistent unexplained cytopenia. Diagnosis of SF3B1-mutant MDS has considerable clinical implications in terms of risk stratification and therapeutic decision making. In fact, this condition has a relatively good prognosis and may respond to luspatercept with abolishment of the transfusion requirement.", "doi": "10.1182/blood.2020004850", "pmid": "32347921", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(20)61895-X"}, {"db": "pmc", "key": "PMC7362582"}], "notes": [], "created": "2020-12-10T14:46:51.952Z", "modified": "2021-11-10T12:49:21.516Z"}, {"entity": "publication", "iuid": "ee0a6224e2a94d9ab542f3537deca12a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee0a6224e2a94d9ab542f3537deca12a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee0a6224e2a94d9ab542f3537deca12a"}}, "title": "Gene expression and risk of leukemic transformation in myelodysplasia.", "authors": [{"family": "Shiozawa", "given": "Yusuke", "initials": "Y", "orcid": "0000-0001-9814-9230", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dc8c5586f854ce38bd2671a7e93285b.json"}}, {"family": "Malcovati", "given": "Luca", "initials": "L", "orcid": "0000-0002-1460-1611", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac37858898774ff29209add33a79fd48.json"}}, {"family": "Gall\u00ec", "given": "Anna", "initials": "A", "orcid": "0000-0002-7912-6428", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2e7029ae6f442b2a8ea6947f9f1989e.json"}}, {"family": "Pellagatti", "given": "Andrea", "initials": "A", "orcid": "0000-0002-6122-0221", "researcher": {"href": "https://publications.scilifelab.se/researcher/744f0150ad6f456bb79b30f7acb2ed2a.json"}}, {"family": "Karimi", "given": "Mohsen", "initials": "M", "orcid": "0000-0002-8946-6944", "researcher": {"href": "https://publications.scilifelab.se/researcher/8353eda283bb4e1391261269d80f9f7f.json"}}, {"family": "Sato-Otsubo", "given": "Aiko", "initials": "A"}, {"family": "Sato", "given": "Yusuke", "initials": "Y", "orcid": "0000-0003-0913-7815", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9da90ff6344440cba83f530ffcddf8e.json"}}, {"family": "Suzuki", "given": "Hiromichi", "initials": "H", "orcid": "0000-0003-1434-7104", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ff5a7c284d4ebea1a03fc0948cc27d.json"}}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T"}, {"family": "Yoshida", "given": "Kenichi", "initials": "K", "orcid": "0000-0001-5189-5105", "researcher": {"href": "https://publications.scilifelab.se/researcher/c92b02588d804081a867f4489139affd.json"}}, {"family": "Shiraishi", "given": "Yuichi", "initials": "Y", "orcid": "0000-0001-6144-5845", "researcher": {"href": "https://publications.scilifelab.se/researcher/a807a9117617477196d55d150e62b437.json"}}, {"family": "Chiba", "given": "Kenichi", "initials": "K"}, {"family": "Makishima", "given": "Hideki", "initials": "H"}, {"family": "Boultwood", "given": "Jacqueline", "initials": "J", "orcid": "0000-0002-4330-2928", "researcher": {"href": "https://publications.scilifelab.se/researcher/389b184fad7048daaa8bd0466b298374.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-0602-3815", "researcher": {"href": "https://publications.scilifelab.se/researcher/f28d2116631f4f4cb286be690e0cf896.json"}}, {"family": "Miyano", "given": "Satoru", "initials": "S", "orcid": "0000-0002-1753-6616", "researcher": {"href": "https://publications.scilifelab.se/researcher/76e65512044c4965863ed41ef8aadd31.json"}}, {"family": "Cazzola", "given": "Mario", "initials": "M", "orcid": "0000-0001-6984-8817", "researcher": {"href": "https://publications.scilifelab.se/researcher/e85ab5f89c604aad824a42107184f196.json"}}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}], "type": "journal article", "published": "2017-12-14", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "130", "issue": "24", "pages": "2642-2653", "issn-l": "0006-4971"}, "abstract": "Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic disorders with a highly variable prognosis. To identify a gene expression-based classification of myelodysplasia with biological and clinical relevance, we performed a comprehensive transcriptomic analysis of myeloid neoplasms with dysplasia using transcriptome sequencing. Unsupervised clustering of gene expression data of bone marrow CD34 + cells from 100 patients identified 2 subgroups. The first subtype was characterized by increased expression of genes related to erythroid/megakaryocytic (EMK) lineages, whereas the second subtype showed upregulation of genes related to immature progenitor (IMP) cells. Compared with the first so-called EMK subtype, the IMP subtype showed upregulation of many signaling pathways and downregulation of several pathways related to metabolism and DNA repair. The IMP subgroup was associated with a significantly shorter survival in both univariate (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.8-14; P = .002) and multivariate analysis (HR, 4.9; 95% CI, 1.3-19; P = .02). Leukemic transformation was limited to the IMP subgroup. The prognostic significance of our classification was validated in an independent cohort of 183 patients. We also constructed a model to predict the subgroups using gene expression profiles of unfractionated bone marrow mononuclear cells (BMMNCs). The model successfully predicted clinical outcomes in a test set of 114 patients with BMMNC samples. The addition of our classification to the clinical model improved prediction of patient outcomes. These results indicated biological and clinical relevance of our gene expression-based classification, which will improve risk prediction and treatment stratification of MDS.", "doi": "10.1182/blood-2017-05-783050", "pmid": "29097382", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(20)32644-6"}], "notes": [], "created": "2018-10-31T13:09:22.884Z", "modified": "2021-06-21T14:57:20.742Z"}]}