作者
Lachelle D Weeks, Abhishek Niroula, Donna Neuberg, Waihay Wong, R Coleman Lindsley, Marlise R Luskin, Nancy Berliner, Richard M Stone, Daniel J DeAngelo, Robert J Soiffer, Md Mesbah Uddin, Gabriel Griffin, Caitlyn Vlasschaert, Christopher J Gibson, Siddhartha Jaiswal, Alexander G Bick, Luca Malcovati, Pradeep Natarajan, Benjamin L Ebert
发表日期
2023/4/25
期刊
NEJM evidence
卷号
2
期号
5
页码范围
EVIDoa2200310
出版商
Massachusetts Medical Society
简介
Background
Clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS) are defined by somatic mutations in genes associated with myeloid neoplasms (MN) at a variant allele fraction (VAF) of 0.02 or greater in the absence and presence of cytopenia, respectively. CHIP/CCUS is highly prevalent in adults, and defining predictors of MN risk would aid clinical management and research.
Methods
We analyzed sequenced exomes of healthy U.K. Biobank participants (N=438,890) in separate derivation and validation cohorts. Genetic mutations, laboratory values, and MN outcomes were used in conditional probability–based recursive partitioning and Cox regression to determine predictors of incident MN. Combined statistical weights were used to define a clonal hematopoiesis risk score (CHRS). Independent CHIP/CCUS patient cohorts were used to test the …
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LD Weeks, A Niroula, D Neuberg, W Wong… - NEJM evidence, 2023