TP53 Mutations Affect Outcomes in MDS With Chromosome 5q Deletion

A subtype of myelodysplastic syndromes (MDS) features isolated deletion of chromosome 5q, or MDS-del(5q). Outcomes in patients with this disease subtype are influenced by TP53 gene mutations and the allelic status of those mutations, a study published in Blood determined.

“Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with MDS,” explained lead study author Maria Julia Montoro, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain.

The study assessed how TP53 mutations affect outcomes, specifically in MDS-del(5q) subtype disease. In a cohort of 682 patients with this diagnosis, investigators searched for TP53 mutations and examined allelic imbalances. Among the patients with TP53 mutations in this cohort, 24% had multihit alterations and 76% had monoallelic mutations.

In patients with TP53 multihit alterations, the alterations were predictive for increased risk of leukemic transformation.

Among the patients with TP53 monoallelic alterations, the study found that the effect from those alterations varied by variant allele frequency (VAF). In patients with VAF of less than 20%, the disease behaved like TP53 wild-type disease. In patients with VAF of 20% or greater, outcomes matched those seen in patients with TP53 multihit alterations.

“This study underscores the importance of considering TP53 allelic state and VAF in the risk stratification and treatment decision-making process for patients with MDS-del(5q),” Dr. Montoro concluded.

Reference

Montoro MJ, Palomo L, Haferlach C, et al. Influence of TP53 gene mutations and its allelic status in myelodysplastic syndromes with isolated 5q deletion. Blood. 2024. doi:10.1182/blood.2024023840