Natural history of clonal haematopoiesis seen in real-world haematology settings

Br J Haematol. 2024 May;204(5):1844-1855. doi: 10.1111/bjh.19423. Epub 2024 Mar 24.


Recursive partitioning of healthy consortia led to the development of the Clonal Hematopoiesis Risk Score (CHRS) for clonal haematopoiesis (CH); however, in the practical setting, most cases of CH are diagnosed after patients present with cytopenias or related symptoms. To address this real-world population, we characterize the clinical trajectories of 94 patients with CH and distinguish CH harbouring canonical DNMT3A/TET2/ASXL1 mutations alone ('sole DTA') versus all other groups ('non-sole DTA'). TET2, rather than DNMT3A, was the most prevalent mutation in the real-world setting. Sole DTA patients did not progress to myeloid neoplasm (MN) in the absence of acquisition of other mutations. Contrastingly, 14 (20.1%) of 67 non-sole DTA patients progressed to MN. CHRS assessment showed a higher frequency of high-risk CH in non-sole DTA (vs. sole DTA) patients and in progressors (vs. non-progressors). RUNX1 mutation conferred the strongest risk for progression to MN (odds ratio [OR] 10.27, 95% CI 2.00-52.69, p = 0.0053). The mean variant allele frequency across all genes was higher in progressors than in non-progressors (36.9% ± 4.62% vs. 24.1% ± 1.67%, p = 0.0064). This analysis in the post-CHRS era underscores the natural history of CH, providing insight into patterns of progression to MN.

Keywords: CHIP; acute myeloid leukaemia; clonal haematopoiesis; epigenetics; myelodysplastic syndrome; myeloid genomics.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clonal Hematopoiesis* / genetics
  • Core Binding Factor Alpha 2 Subunit / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methyltransferase 3A
  • DNA-Binding Proteins* / genetics
  • Dioxygenases*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / genetics


  • TET2 protein, human
  • DNA-Binding Proteins
  • Dioxygenases
  • DNA Methyltransferase 3A
  • DNMT3A protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Proto-Oncogene Proteins
  • ASXL1 protein, human
  • Repressor Proteins
  • DNA (Cytosine-5-)-Methyltransferases