p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q) | Aplastic Anemia and MDS International Foundation

p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q)

Journal Title: 
Haematologica
Author(s): 
Saft L, Karimi M, Ghaderi M, Matolcsy A, Mufti GJ, Kulasekararaj A, Göhring G, Giagounidis A, Selleslag D, Muus P, Sanz G, Mittelman M, Bowen D, Porwit A, Fu T, Backstrom J, Fenaux P, Macbeth KJ, Hellström-Lindberg E
Primary Author: 
Saft L
Original Publication Date: 
Friday, March 28, 2014

International Prognostic Scoring System-defined Low- or Intermediate-1-risk (lower-risk) del(5q) myelodysplastic syndromes are considered to have an indolent course; however, recent data have identified a subgroup of patients with more aggressive disease and poorer outcomes. Using deep sequencing technology, we previously demonstrated that 18% of patients with lower-risk del(5q) myelodysplastic syndromes carry TP53 mutated subclones rendering them at higher risk for progression. In this study, bone marrow biopsies from 85 patients treated with lenalidomide in the MDS-004 clinical trial were retrospectively assessed for p53 expression by immunohistochemistry in association with outcome. Strong p53 expression in ≥1% of bone marrow progenitor cells, observed in 35% (30 of 85) of patients, was significantly associated with higher acute myeloid leukemia risk (P=0.0006), shorter overall survival (P=0.0175), and a lower cytogenetic response rate (P=0.009), but not with achievement or duration of 26-week transfusion independence response. In a multivariate analysis, p53-positive immunohistochemistry was the strongest independent predictor of transformation to acute myeloid leukemia (P=0.0035). Pyrosequencing analysis of laser-microdissected cells with strong p53 expression confirmed TP53 mutation, whereas cells with moderate expression were predominantly of wild-type p53. This study validates p53 immunohistochemistry as a strong and clinically useful predictive tool in patients with lower-risk del(5q) myelodysplastic syndromes. This study is based on data from the MDS 004 trial (clinicaltrials.gov identifier: NCT00179621).

Bone Marrow Diseases: