Karyotypic complexity and mutated TP53 are associated with myeloid neoplasms with ring chromosomes

This study evaluated the prevalence of ring chromosomes, their association with TP53 alterations, and their prognostic impact in myeloid neoplasms.

A retrospective analysis of 12,935 onco-hematological karyotypes from 2017-2022 identified 21 adult patients with myeloid neoplasms harboring ring chromosomes. Fluorescence in situ hybridization was used to assess TP53 deletions, while next-generation sequencing detected TP53 mutations.

Ring chromosomes were identified in 0.29% of the cases. The median patient age was 69 years and 67% were male. Acute myeloid leukemia and myelodysplastic neoplasms were the most frequent diagnoses. The median number of karyotypic abnormalities was nine (range: 1-28). Karyotypic complexity, TP53 deletions, mutations, and multi-hit alterations were observed in 81%, 19%, 78%, and 61% of the cases, respectively. ring chromosomes were most frequently derived from chromosomes 6 and 7. Median overall survival was 3.2 months. TP53 multi-hit alterations (Hazard ratio: 10.63; p-value = 0.001) and the number of karyotypic abnormalities (Hazard ratio: 1.06; p-value = 0.043) were significantly associated with increased mortality. Patients with very complex karyotypes had a 5.53-fold higher risk of death.

Ring chromosomes are rare in myeloid neoplasms and are consistently associated with high karyotypic complexity and TP53 alterations. In this cohort, both TP53 alterations and karyotypic complexity emerged as independent prognostic factors and were strongly associated with an extremely poor prognosis.