Expression of p53 protein isoforms predicts survival in patients with multiple myeloma

Loss and/or mutation of the TP53 gene are associated with short survival in multiple myeloma, but the p53 landscape goes far beyond. At least 12 p53 protein isoforms have been identified as a result of a combination of alternative splicing, alternative promoters and/or alternative transcription site starts, which are grouped as α, β, γ, from transactivation domain (TA), long, and short isoforms. Nowadays, there are no studies evaluating the expression of p53 isoforms and its clinical relevance in multiple myeloma (MM). We used capillary nanoimmunoassay to quantify the expression of p53 protein isoforms in CD138-purified samples from 156 patients with newly diagnosed MM who were treated as part of the PETHEMA/GEM2012 clinical trial and investigated their prognostic impact. Quantitative real-time polymerase chain reaction was used to corroborate the results at RNA levels. Low and high levels of expression of short and TAp53β/γ isoforms, respectively, were associated with adverse prognosis in MM patients. Multivariate Cox models identified high levels of TAp53β/γ (hazard ratio [HR], 4.49; p
The Instituto de Salud Carlos III, European Union FEDER funds, Grant Numbers: PI16/01074 and PI19/00674; The Asociación Española Contra el Cáncer, Grant Number: AECC, PROYE20047GUTI; National Science Centre, Poland, Grant Number: UMO-2019/35/B/NZ5/02824; The Consejería de Educación de Castilla y León and FEDER funds; AECC, Grant Number: CLJUN18010DERA.