Clinical relevance of clonal hematopoiesis in the oldest-old population.

作者：M. Rossi, M. Meggendorfer, M. Zampini, M. Tettamanti, E. Riva, E. Travaglino, M. Bersanelli, S. Mandelli, A. Galbussera, E. Mosca, Elena Saba, C. Chiereghin, N. Manes, C. Milanesi, M. Ubezio, L. Morabito, C. Peano, G. Soldà, R. Asselta, S. Duga, C. Selmi, M. De Santis, K. Malik, G. Maggioni, M. Bicchieri, A. Campagna, C. Tentori, Antonio Russo, E. Civilini, P. Allavena, R. Piazza, G. Corrao, C. Sala, A. Termanini, L. Giordano, P. Detoma, A. Malabaila, Luca Sala, S. Rosso, R. Zanetti, C. Saitta, E. Riva, G. Condorelli, F. Passamonti, A. Santoro, F. Solé, U. Platzbecker, P. Fenaux, N. Bolli, G. Castellani, W. Kern, G. Vassiliou, T. Haferlach, U. Lucca, M. D. della Porta · 发表于：Blood · 年份：2021 · DOI：10.1182/blood.2021011320 · 被引用次数：45 · 研究领域：Medicine

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes very common in oldest-old individuals, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 oldest-old individuals enrolled in two population-based studies and investigate the relationships between CHIP and associated pathologies. Clonal mutations were observed in one third of oldest-old individuals and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, ASXL1 with additional genetic lesions) and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1 or JAK2 (most occurring as single lesion) were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was a common finding in oldest-old population, the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly-specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordin...