Among patients with clonal cytopenia of undetermined significance (CCUS), morphologic dysplasia may be linked with transition to myelodysplastic syndrome (MDS), according to research published in the European Journal of Haematology.
Clonal hematopoiesis of indeterminate potential (CHIP), in which blood cells harbor cytogenetic abnormalities or somatic mutations, is present in about 10% of individuals older than 70 years. In the presence of unexplained cytopenia, CHIP is instead referred to as CCUS and, as with CHIP, is associated with progression to hematologic malignancy. The risk of transition to disease is, however, much higher with CCUS than with CHIP, at approximately 80% over 5 years in the former vs 1% per year in the latter.
Because the risk of malignancy transition is so high among patients with CCUS, identification of markers indicative of MDS risk is critical. For this study, researchers evaluated any clinical, histologic, or molecular factors that may help to predict risk of disease transition to MDS among patients with CCUS, hypothesizing that low-level morphologic dysplasia may be one such predictive marker.
Overall, the researchers reviewed the results of bone marrow biopsies from 49 patients with CCUS and 49 patients with MDS. Of patients with CCUS, 24 had no dysplasia (CCUS-ND) and 25 had dysplasia (CCUS-D). The average ages in the CCUS-ND, CCUS-D, and MDS groups were 74.4, 76.4, and 72.9 years, respectively; 54%, 72%, and 74% were men; 63%, 60%, and 60% had a history of smoking; and 46%, 64%, and 92% had evidence of hypercellular bone marrow.
Compared with patients in the CCUS-ND group, patients with CCUS-D showed no significant difference in degree of cytopenia, bone marrow cellularity, or rate of presence of flow cytometric abnormality. Patients with CCUS-D were, however, more likely to have mutations in genes associated with malignancy, including non-TET2/DNMT3A/ASXL1 variants, spliceosome variants, and IDH2/RUNX1/CBL.
Although bone marrow hypercellularity was significantly different between the MDS and CCUS-ND groups, no such difference was found between the MDS and CCUS-D groups.
“In conclusion, our findings and those of others support the notion that CCUS with dysplasia more closely resembles MDS than CCUS without dysplasia, and we propose a model in which clonal expansion and acquisition of further mutations result in a linear progression from CHIP to CCUS-ND, then to CCUS-D, which is the immediate precursor to MDS,” the authors wrote.
Jajosky AN, Sadri N, Meyerson HJ, et al. Clonal cytopenia of undetermined significance (CCUS) with dysplasia is enriched for MDS-type molecular findings compared to CCUS without dysplasia. Eur J Haematol. Published online January 1, 2021. doi:10.1111/ejh.13574