Sökning: (WFRF:(De Andrade Mariza)) lar1:(lu) > Aberrant activation...
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000 | 09250naa a2201849 4500 | |
001 | oai:gup.ub.gu.se/325109 | |
003 | SwePub | |
008 | 240528s2023 | |||||||||||000 ||eng| | |
009 | oai:lup.lub.lu.se:51babf53-932c-4d12-9728-7617d858c9b0 | |
024 | 7 | a https://gup.ub.gu.se/publication/3251092 URI |
024 | 7 | a https://doi.org/10.1038/s41586-023-05806-12 DOI |
024 | 7 | a https://lup.lub.lu.se/record/51babf53-932c-4d12-9728-7617d858c9b02 URI |
040 | a (SwePub)gud (SwePub)lu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Weinstock, Joshua Su University of Michigan4 aut |
245 | 1 0 | a Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis. |
264 | 1 | c 2023 |
520 | a Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
653 | a animal | |
653 | a clonal hematopoiesis | |
653 | a genetics | |
653 | a genome-wide association study | |
653 | a hematopoiesis | |
653 | a hematopoietic stem cell | |
653 | a human | |
653 | a metabolism | |
653 | a mouse | |
653 | a mutation | |
653 | a Animals | |
653 | a Clonal Hematopoiesis | |
653 | a Genome-Wide Association Study | |
653 | a Hematopoiesis | |
653 | a Hematopoietic Stem Cells | |
653 | a Humans | |
653 | a Mice | |
653 | a Mutation | |
700 | 1 | a Smith, J.G.u Gothenburg University,Göteborgs universitet,University of Gothenburg,Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Heart Failure and Mechanical Support,Forskargrupper vid Lunds universitet,Molecular Epidemiology and Cardiology,Cardiovascular Epigenetics,WCMM- Wallenberg center för molekylär medicinsk forskning,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Skåne University Hospital,Sahlgrenska University Hospital,Stanford University School of Medicine,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xsmigu |
700 | 1 | a Burugula, Bala Bharathiu Bloodworks Northwest Research Institute,Skåne University Hospital,Lund University4 aut |
700 | 1 | a Uddin, Md Mesbah4 aut |
700 | 1 | a Jahn, Nikolaus4 aut |
700 | 1 | a Belk, Julia A4 aut |
700 | 1 | a Bouzid, Hind4 aut |
700 | 1 | a Daniel, Bence4 aut |
700 | 1 | a Miao, Zhuang4 aut |
700 | 1 | a Ly, Nghi4 aut |
700 | 1 | a Mack, Taralynn M4 aut |
700 | 1 | a Luna, Sofia E4 aut |
700 | 1 | a Prothro, Katherine P4 aut |
700 | 1 | a Mitchell, Shaneice R4 aut |
700 | 1 | a Laurie, Cecelia A4 aut |
700 | 1 | a Broome, Jai G4 aut |
700 | 1 | a Taylor, Kent D4 aut |
700 | 1 | a Guo, Xiuqing4 aut |
700 | 1 | a Sinner, Moritz F4 aut |
700 | 1 | a von Falkenhausen, Aenne S4 aut |
700 | 1 | a Kääb, Stefan4 aut |
700 | 1 | a Shuldiner, Alan R4 aut |
700 | 1 | a O'Connell, Jeffrey R4 aut |
700 | 1 | a Lewis, Joshua P4 aut |
700 | 1 | a Boerwinkle, Eric4 aut |
700 | 1 | a Barnes, Kathleen C4 aut |
700 | 1 | a Chami, Nathalie4 aut |
700 | 1 | a Kenny, Eimear E4 aut |
700 | 1 | a Loos, Ruth J F4 aut |
700 | 1 | a Fornage, Myriam4 aut |
700 | 1 | a Hou, Lifang4 aut |
700 | 1 | a Lloyd-Jones, Donald M4 aut |
700 | 1 | a Redline, Susan4 aut |
700 | 1 | a Cade, Brian E4 aut |
700 | 1 | a Psaty, Bruce M4 aut |
700 | 1 | a Bis, Joshua C4 aut |
700 | 1 | a Brody, Jennifer A4 aut |
700 | 1 | a Silverman, Edwin K4 aut |
700 | 1 | a Yun, Jeong H4 aut |
700 | 1 | a Qiao, Dandi4 aut |
700 | 1 | a Palmer, Nicholette D4 aut |
700 | 1 | a Freedman, Barry I4 aut |
700 | 1 | a Bowden, Donald W4 aut |
700 | 1 | a Cho, Michael H4 aut |
700 | 1 | a DeMeo, Dawn L4 aut |
700 | 1 | a Vasan, Ramachandran S4 aut |
700 | 1 | a Yanek, Lisa R4 aut |
700 | 1 | a Becker, Lewis C4 aut |
700 | 1 | a Kardia, Sharon L R4 aut |
700 | 1 | a Peyser, Patricia A4 aut |
700 | 1 | a He, Jiang4 aut |
700 | 1 | a Rienstra, Michiel4 aut |
700 | 1 | a Van der Harst, Pim4 aut |
700 | 1 | a Kaplan, Robert4 aut |
700 | 1 | a Heckbert, Susan R4 aut |
700 | 1 | a Smith, Nicholas L4 aut |
700 | 1 | a Wiggins, Kerri L4 aut |
700 | 1 | a Arnett, Donna K4 aut |
700 | 1 | a Irvin, Marguerite R4 aut |
700 | 1 | a Tiwari, Hemant4 aut |
700 | 1 | a Cutler, Michael J4 aut |
700 | 1 | a Knight, Stacey4 aut |
700 | 1 | a Muhlestein, J Brent4 aut |
700 | 1 | a Correa, Adolfo4 aut |
700 | 1 | a Raffield, Laura M4 aut |
700 | 1 | a Gao, Yan4 aut |
700 | 1 | a de Andrade, Mariza4 aut |
700 | 1 | a Rotter, Jerome I4 aut |
700 | 1 | a Rich, Stephen S4 aut |
700 | 1 | a Tracy, Russell P4 aut |
700 | 1 | a Konkle, Barbara A4 aut |
700 | 1 | a Johnsen, Jill Mu Bloodworks Northwest Research Institute,Skåne University Hospital,Lund University4 aut |
700 | 1 | a Wheeler, Marsha M4 aut |
700 | 1 | a Smith, J. Gustav,d 1982u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xsmigu |
700 | 1 | a Melander, O.u Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups4 aut0 (Swepub:lu)endo-ome |
700 | 1 | a Nilsson, P.M.u Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups4 aut0 (Swepub:lu)medf-pni |
700 | 1 | a Custer, Brian S4 aut |
700 | 1 | a Duggirala, Ravindranath4 aut |
700 | 1 | a Curran, Joanne E4 aut |
700 | 1 | a Blangero, John4 aut |
700 | 1 | a McGarvey, Stephen4 aut |
700 | 1 | a Williams, L Keoki4 aut |
700 | 1 | a Xiao, Shujie4 aut |
700 | 1 | a Yang, Mao4 aut |
700 | 1 | a Gu, C Charles4 aut |
700 | 1 | a Chen, Yii-Der Ida4 aut |
700 | 1 | a Lee, Wen-Jane4 aut |
700 | 1 | a Marcus, Gregory M4 aut |
700 | 1 | a Kane, John P4 aut |
700 | 1 | a Pullinger, Clive R4 aut |
700 | 1 | a Shoemaker, M Benjamin4 aut |
700 | 1 | a Darbar, Dawood4 aut |
700 | 1 | a Roden, Dan M4 aut |
700 | 1 | a Albert, Christine4 aut |
700 | 1 | a Kooperberg, Charles4 aut |
700 | 1 | a Zhou, Ying4 aut |
700 | 1 | a Manson, JoAnn E4 aut |
700 | 1 | a Desai, Pinkal4 aut |
700 | 1 | a Johnson, Andrew D4 aut |
700 | 1 | a Mathias, Rasika A4 aut |
700 | 1 | a Blackwell, Thomas W4 aut |
700 | 1 | a Abecasis, Goncalo R4 aut |
700 | 1 | a Smith, Albert V4 aut |
700 | 1 | a Kang, Hyun M4 aut |
700 | 1 | a Satpathy, Ansuman T4 aut |
700 | 1 | a Natarajan, Pradeep4 aut |
700 | 1 | a Kitzman, Jacob O4 aut |
700 | 1 | a Whitsel, Eric A4 aut |
700 | 1 | a Reiner, Alexander P4 aut |
700 | 1 | a Bick, Alexander G4 aut |
700 | 1 | a Jaiswal, Siddhartha4 aut |
710 | 2 | a University of Michiganb Kardiologi4 org |
773 | 0 | t Natureg 616:7958, s. 755-763q 616:7958<755-763x 1476-4687 |
856 | 4 | u http://dx.doi.org/10.1038/s41586-023-05806-1y FULLTEXT |
856 | 4 8 | u https://gup.ub.gu.se/publication/325109 |
856 | 4 8 | u https://doi.org/10.1038/s41586-023-05806-1 |
856 | 4 8 | u https://lup.lub.lu.se/record/51babf53-932c-4d12-9728-7617d858c9b0 |
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