Particular drivers of clonal hematopoiesis are associated with a higher chance of developing myelodysplastic syndromes (MDS) and may yield significant changes in blood cell parameters, a study published in Nature Genetics suggested.

The study included the medical records of 454,340 UK Biobank participants with clonal cytopenia of undetermined significance divided into 2 independent cohorts. Of all participants, 1,808 developed a myeloid neoplasm 0 to 15 years after recruitment.

The researchers evaluated different mutations in clonal hematopoiesis as well as hematology and biochemistry test parameters among individuals who later developed MDS in comparison with healthy participants.

They constructed and validated Cox regression models quantifying the risk of progression to each myeloid neoplasm subtype as well as a “myelodysplastic syndromes-predict” web application that generates time-dependent predictions with the input of basic blood tests and genetic data.

Read more about MDS etiology

“We observed varying strengths of association between particular gene mutations and each of the 3 myeloid neoplasm subtypes. For example, SF3B1 mutations were substantially associated with a higher risk of MDS, while SRSF2 mutations were substantially associated with all myeloid neoplasm subtypes, with SRSF2/TET2 commutated cases were more likely to develop MDS and SRSF2/IDH2 commutated cases were more likely to develop acute myeloid leukemia. Also, DNMT3A R882 mutations were specifically associated with acute myeloid leukemia,” the researchers explained.

Recent evidence suggests that MDS can be predicted years in advance by particular genetic characteristics, offering hope for preventive therapies as an alternative to actual treatment.


Gu M, Kovilakam SC, Dunn WG, et al. Multiparameter prediction of myeloid neoplasia riskNat Genet. Published online August 24, 2023. doi:10.1038/s41588-023-01472-1