A new prognostic index to make short-term prognoses in MDS patients treated with azacitidine: A combination of p53 expression and cytogenetics

Leuk Res. 2016 Feb:41:21-6. doi: 10.1016/j.leukres.2015.11.014. Epub 2015 Nov 25.

Abstract

TP53 mutation is associated with various hematological malignancies and immunohistochemistry of p53 has been used as a simple method to establish the presence of a TP53 mutation. Since the significance of p53 expression is controversial in myelodysplastic syndrome (MDS) patients treated with azacitidine (Aza), we analyzed the prevalence of p53 expression as a prognostic factor in 60 MDS patients treated with Aza. To assess p53 expression, immunohistochemical analyses of bone marrow clot sections were performed. Overall survival (OS) was significantly lower in p53-positive patients compared with p53-negetive patients (59% vs. 85% at 12 months; P=0.006). Multivariate analysis demonstrated that p53-positive was a significant prognostic factor for OS along with poor cytogenetics. Here, we propose a new prognostic index to make short-term prognoses of MDS patients in the era of Aza treatment; high: p53-positive and poor cytogenetics, low: p53-negative and absence of poor cytogenetics, and intermediate: the others. OS was significantly different among the three groups according to this index (Low 92%, Intermediate 65% and High 27% at 12 months; P<0.0001). In conclusion, p53 expression was a significant prognostic factor in MDS patients treated with Aza. In combination with cytogenetic abnormalities, it is possible to make short-term prognoses.

Keywords: Azacitidine; Myelodysplastic syndrome; Prognostic index; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Chromosome Aberrations
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Prognosis
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Azacitidine