Clinical Characteristics and Outcomes of CCUS With ZRSR2 Mutations

ZRSR2 mutations in clonal cytopenia of undetermined significance (CCUS) were associated with male sex, with a significant subset showing concurrent hematologic malignancies or chromosomal abnormalities. Median overall survival (mOS) was better for patients with ZRSR2-mutated CCUS with the favorable co-mutation, TET2.

The occurrence of CCUS often results in a progression into myeloid neoplasms (MNs). CCUS is defined as the presence of any ongoing cytopenia and myeloid malignancy–associated gene mutations. This retrospective study presented by Mahmoud Yacout, MD, Mayo Clinic, Rochester, Minnesota, examined the clinical characteristics of patients with CCUS and ZRSR2 mutations and compared this population’s survival with that of ZRSR2-positive patients with MNs or myelodysplastic syndrome (MDS).

The investigators analyzed next-generation sequencing results from Mayo Clinic patients between 2016 and 2023. Of 9,320 patients, 39 had ZRSR2 mutations, all of whom were male. Of these 39, eight patients also had hematologic malignancies, 11 had chromosomal abnormalities, and 23 had an absolute monocyte count greater than 0.5 × 10⁹/L.

When compared with a control cohort of 125 patients who had ZRSR2 mutations with either MDS or myeloproliferative neoplasms, patients with CCUS showed a trend toward better mOS (30 months vs 56 months; P=.14). When the investigators excluded acute myeloid leukemia cases from the comparison, the control cohort had an mOS of 39 months compared with the CCUS mOS of 30 months (P=.24). Patients with CCUS and a co-occurring TET2 mutation had better mOS than those without (mOS not reached vs 41 mOS; P=.02).

Overall, some patients with ZRSR2-mutated CCUS had concurrent blood-related cancers or disorders, and others had protective co-mutations, specifically TET2. Both could influence clinical outcomes and treatment approaches.

Reference

Yacout M, Katamesh B, Jabban Y, et al. A clinical overview of clonal cytopenia of undetermined significance in the presence of ZRSR2 mutations. Abstract #2667. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.