CLONAL monocytosis risk prediction has been strengthened by new population-level data demonstrating that specific clonal blood states are strongly associated with myeloid malignancy and adverse health outcomes.
Clonal monocytosis of undetermined significance and clonal cytopenia and monocytosis of undetermined significance represent distinct conditions within the broader spectrum of clonal haematopoiesis, particularly in individuals who do not meet diagnostic criteria for chronic myelomonocytic leukaemia.
In a large cohort of 431,531 participants, researchers analysed clinical, genomic, and health outcome data to evaluate the prevalence and natural history of these conditions.
The findings indicate that both conditions are high-risk states associated with incident myeloid neoplasia, as well as cardiovascular and renal disease. These results establish their clinical relevance and highlight the importance of recognising them as separate entities in routine practice.
Refining Diagnostic Definitions
The study further demonstrated that refining diagnostic criteria improves the predictive value of clonal monocytosis risk prediction. Incorporating sex-specific monocyte thresholds enhanced risk stratification, reflecting known differences in monocyte counts between men and women.
In addition, excluding isolated mutations in DNMT3A from the definition significantly strengthened the association with incident myeloid neoplasia. These refinements address variability in disease progression and allow for a more precise identification of individuals at higher risk. The findings suggest that current classification frameworks can be optimised to improve prognostic accuracy and clinical utility.
Machine Learning Enhances Detection
To support clinical application, researchers developed a machine learning classifier capable of predicting the presence of SRSF2 mutations, which are associated with increased risk of myeloid neoplasia. The model, based solely on complete blood count indices, enables identification of high-risk individuals without requiring advanced genomic testing.
Validation in an independent cohort of 625,328 primary care patients confirmed the robustness of the findings. Together, these results underscore the value of clonal monocytosis risk prediction as a tool for early identification of individuals at risk of serious haematological and systemic disease.
Reference
Dunn WG et al. The prevalence and clinical significance of clonal monocytosis. Blood. Blood. 2026; blood.2025031883. doi: https://doi.org/10.1182/blood.2025031883.
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