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

Haematologica. 2014 Jun;99(6):1041-9. doi: 10.3324/haematol.2013.098103. Epub 2014 Mar 28.


Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring System as low- or intermediate-1-risk (lower-risk) are considered to have an indolent course; however, recent data have identified a subgroup of these 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 of 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 the TP53 mutation, whereas cells with moderate expression predominantly had 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 was based on data from the MDS 004 trial (clinicaltrials.gov identifier: NCT00179621).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 5*
  • Disease Progression
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Leukemia, Myeloid, Acute
  • Mutation
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Patient Outcome Assessment
  • Prognosis
  • Reproducibility of Results
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism


  • Tumor Suppressor Protein p53

Associated data

  • ClinicalTrials.gov/NCT00179621