A research team from the CIBER Cancer Division (CIBERONC) at the Salamanca University HealthcareComplex–Salamanca Biomedical Research Institute (IBSAL) and the Cancer Research Center (USAL-CSIC), led by hematologist Norma C. Gutiérrez, has identified alterations in the regulation of post-translational modifications of the p53 protein that may help predict the clinical course of patients with multiple myeloma, one of the most common blood cancers. The results, published in the journal *Blood Cancer Journal*, demonstrate that certain post-translational modifications of the p53 protein provide prognostic information independently of alterations in the TP53 gene, which is considered one of the main markers of poor prognosis in this disease.
The p53 protein plays an essential role in protecting cells from DNA damage and in preventing tumor development. Although alterations in the TP53 gene can prevent this protein from functioning properly, its activity can also be affected by post-translational modifications—small chemical changes that regulate its stability and its ability to respond to cellular damage.
In this study, the research team analyzed samples collected at the time of diagnosis from 127 patients with multiple myeloma who were treated according to the GEM2012 protocol of the Spanish Myeloma Group. Using a highly sensitive technique called capillary nanoimmunoassay, they quantified four post-translational modifications of the p53 protein—three phosphorylations and one acetylation—that are involved in regulating its activity.
“The results revealed considerable variability among patients. In addition, those with biallelic inactivation of the TP53 gene had significantly lower levels of some of these modifications ” explains Elizabeta A. Rojas, the study’s lead author and a CIBERONC researcher at CIC/IBSAL. Furthermore, lower p53 phosphorylation was associated with a higher risk of disease progression.
The collaborative study, involving several groups from CIBERONC, also analyzed other components of the DNA damage response, such as the γH2AX marker , the Chk2 kinase, and the PP1A and PP2A-C phosphatases. Alterations in these proteins suggest that the mechanisms regulating the phosphorylation status of p53 may be compromised in some patients, contributing to the loss of its function, even in the absence of genetic alterations in TP53.
“This is the first study to systematically analyze post-translational modifications of the p53 protein in a large cohort of patients with multiple myeloma. The findings show that the regulation of p53 plays a significant role in the clinical course of the disease and suggest that the evaluation of these modifications could complement genetic analysis of TP53 to improve prognostic stratification of patients,” concludes the research team.
The study received public funding from the Carlos III Health Institute (PI23/00319) and the Castilla y León Regional Health Authority (GRS3044/A1/2024). In addition, Elizabeta A. Rojas has received support from the Spanish Foundation for Hematology and Hemotherapy (FEHH) as part of the FEHH’s 2024 call for research grants.
Article reference:
Rojas EA, Cristóbal-Vargas S, Becerro-Recio D, De Ramón C, Cuadrado M, Isidro I, Misiewicz-Krzeminska I, Martínez-López J, Oriol A, Rosiñol L, Lahuerta JJ, San Miguel JF, Mateos MV, Corchete LA, Gutiérrez NC. Study of Post-Translational Modifications of p53 in Multiple Myeloma. Blood Cancer J. July 17, 2026. doi: 10.1038/s41408-026-01568-x. Published online ahead of print. PMID: 42469225.
