PRIMA-1 induces apoptosis in acute myeloid leukaemia cells with p53 gene deletion

Br J Haematol. 2006 Jan;132(2):230-6. doi: 10.1111/j.1365-2141.2005.05851.x.


The p53 tumour suppressor gene located on chromosome 17p13 is the most frequently mutated gene in human tumours. About 5-8% of cases with acute myeloid leukaemia (AML) carry the p53 mutation. Recently, the compound p53-dependent reactivation and induction of massive apoptosis (PRIMA-1) has been shown to induce cytotoxic effects and apoptosis in human tumour cells by restoration of the transcriptional activity of mutated p53. This is believed to be mediated by a change in the conformation of mutated p53 protein, restoring DNA binding and activation of p53 target genes. We studied the effects of PRIMA-1 and commonly used antileukaemic drugs on AML cells from 62 patients. Cells were obtained from peripheral blood or bone marrow and were exposed to PRIMA-1, cytarabine, daunorubicin, chlorodeoxyadenosine and fludarabine. This study showed that PRIMA-1 had cytotoxic effects on AML cells. Conventional AML drugs were less effective in cells with hemizygous p53 deletion. Interestingly, our data indicated that PRIMA-1 was more effective in this subgroup of patients compared with patients with normal chromosome 17. Our data suggest that the concept of restoration of p53 protein by PRIMA-1 or a PRIMA-1-based new drug may increase the efficacy of AML treatment in patients with p53 mutations.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Aza Compounds / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Female
  • Gene Deletion*
  • Genes, p53*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Aza Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Neoplasm Proteins
  • 2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one