Clonal cytopenia of undetermined significance (CCUS) with dysplasia is enriched for MDS‐type molecular findings compared to CCUS without dysplasia. (15th January 2021) - Jajosky, Audrey N.
Abstract: Objectives: Although morphologic dysplasia is not typically considered a feature of CCUS, we have consistently observed low‐level bone marrow (BM) dysplasia among CCUS patients. We sought to determine whether sub‐diagnostic BM dysplasia in CCUS patients is associated with other clinico‐pathologic findings of myelodysplastic syndrome (MDS). Methods: We identified 49 CCUS patients, 25 with sub‐diagnostic dysplasia (CCUS‐D), and 24 having no dysplasia (CCUS‐ND). We compared the clinical, histologic, and laboratory findings of CCUS‐D and CCUS‐ND patients to 49 MDS patients, including blood cell counts, BM morphology, flow cytometry, cytogenetics, and results of next‐generation sequencing. Results: No statistically significant differences were observed between CCUS‐D and CCUS‐ND patients in the degree of cytopenias, BM cellularity, myeloid‐to‐erythroid ratio, or the presence of flow cytometric abnormalities. However, compared to CCUS‐ND, CCUS‐D patients exhibited increased mutations in myeloid malignancy‐associated genes, including non‐ TET2 / DNMT3A / ASXL1 variants, spliceosome ( SF3B1, SRSF2, ZRSR2, or U2AF1 ) variants, and IDH2/RUNX1/CBL variants. CCUS‐D patients were also enriched for higher variant allele frequencies and co‐mutation of TET2 / DNMT3A / ASXL1 with other genes. Conclusions: CCUS‐D patients exhibit a molecular (but not clinical) profile more similar to MDS patients than CCUS‐ND, suggesting CCUS‐D may represent a more immediate precursor to MDS and may warrant closer clinical follow‐up.