Multiparameter prediction of myeloid neoplasia risk

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.