Multiparameter prediction of myeloid neoplasia risk.

Autor: Gu M; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Kovilakam SC; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Dunn WG; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Marando L; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Barcena C; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK.; Department of Biochemistry and Molecular Biology, Universidad de Oviedo, Oviedo, Spain., Mohorianu I; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK., Smith A; Epidemiology and Cancer Statistics Group, University of York, York, UK., Kar SP; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Section of Translational Epidemiology, Division of Population Health Sciences, Bristol, Medical School, University of Bristol, Bristol, UK.; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK., Fabre MA; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK.; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Gerstung M; Division of Artificial Intelligence in Oncology, DKFZ, Heidelberg, Germany., Cargo CA; Haematological Malignancy Diagnostic Service, St James's Hospital, Leeds, UK.; Department of Haematology, Leeds Teaching Hospitals, Leeds, UK., Malcovati L; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Department of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Quiros PM; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. pmquiros@ispasturias.es.; Department of Haematology, University of Cambridge, Cambridge, UK. pmquiros@ispasturias.es.; Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain. pmquiros@ispasturias.es., Vassiliou GS; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. gsv20@cam.ac.uk.; Department of Haematology, University of Cambridge, Cambridge, UK. gsv20@cam.ac.uk.; Department of Haematology, Cambridge University Hospitals NHS Trust, Cambridge, UK. gsv20@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2023 Sep; Vol. 55 (9), pp. 1523-1530. Date of Electronic Publication: 2023 Aug 24.
DOI: 10.1038/s41588-023-01472-1
Abstrakt: The myeloid neoplasms encompass acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Most cases arise from the shared ancestor of clonal hematopoiesis (CH). Here we analyze data from 454,340 UK Biobank participants, of whom 1,808 developed a myeloid neoplasm 0-15 years after recruitment. We describe the differences in CH mutational landscapes and hematology/biochemistry test parameters among individuals that later develop myeloid neoplasms (pre-MN) versus controls, finding that disease-specific changes are detectable years before diagnosis. By analyzing differences between 'pre-MN' and controls, we develop and validate Cox regression models quantifying the risk of progression to each myeloid neoplasm subtype. We construct 'MN-predict', a web application that generates time-dependent predictions with the input of basic blood tests and genetic data. Our study demonstrates that many individuals that develop myeloid neoplasms can be identified years in advance and provides a framework for disease-specific prognostication that will be of substantial use to researchers and physicians.
(© 2023. The Author(s).)
Databáze: MEDLINE
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