AI Article Synopsis

  • Clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS) are conditions characterized by genetic mutations linked to blood cancers, with CHIP being more common in healthy adults while CCUS involves low blood cell counts.
  • Researchers analyzed genetic data from nearly 440,000 participants to identify factors that predict progression to myeloid neoplasms (MN), leading to the development of a clonal hematopoiesis risk score (CHRS).
  • The CHRS effectively categorizes patients into low, intermediate, and high-risk groups, showing that most complications from MN occur within the high-risk category, thus aiding in better clinical management and understanding the conditions.

Article Abstract

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) ≥ 0.02, 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 UK Biobank (UKB) 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 defined a clonal hematopoiesis risk score (CHRS). Independent CHIP/CCUS patient cohorts were used to test prognostic capability of the CHRS in the clinical setting.

Results: Recursive partitioning distinguished CHIP/CCUS cases with 10-year probabilities of MN ranging from 0.0078 - 0.85. Multivariable analysis validated partitioning variables as predictors of MN. Key features, including single mutations, high risk mutations, ≥ 2 mutations, VAF ≥ 0.2, age ≥ 65 years, CCUS vs CHIP and red blood cell indices, influenced MN risk in variable direction. The CHRS defined low risk (n = 10018, 88.4%), intermediate risk (n = 1196, 10.5%), and high risk (n = 123, 1.1%) groups. In clinical cohorts, most MN events occurred in high risk CHIP/CCUS patients.

Conclusions: The CHRS provides simple prognostic framework for CHIP/CCUS, distinguishing a high risk minority from the majority of CHIP/CCUS which has minimal risk for progression to MN.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361696PMC
http://dx.doi.org/10.1056/evidoa2200310DOI Listing

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