The expression of DeltaNTP73, TATP73 and TP53 genes in acute myeloid leukaemia is associated with recurrent cytogenetic abnormalities and in vitro susceptibility to cytarabine cytotoxicity

Br J Haematol. 2008 Jul;142(1):74-8. doi: 10.1111/j.1365-2141.2008.07160.x. Epub 2008 Apr 17.

Abstract

TP73 encodes for two proteins: full-length TAp73 and DeltaNp73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TATP73 and DeltaNTP73 expression in acute myeloid leukaemia (AML) samples and normal CD34(+) progenitors. Both forms were more highly expressed in leukaemic cells. Amongst AML blasts, TATP73 was more expressed in AML harbouring the recurrent genetic abnormalities (RGA): PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11, whereas higher DeltaNTP73 expression was detected in non-RGA cases. TP53 expression did not vary according to DeltaNTP73/TATP73 expression ratio. Leukaemic cells with higher DeltaNTP73/TATP73 ratios were significantly more resistant to cytarabine-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Apoptosis / drug effects
  • Chromosome Aberrations
  • Cytarabine / therapeutic use*
  • DNA-Binding Proteins / genetics*
  • Drug Resistance, Neoplasm
  • Gene Expression
  • Gene Rearrangement
  • Genes, p53 / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Nuclear Proteins / genetics*
  • Polymerase Chain Reaction
  • Recurrence
  • Tumor Suppressor Proteins / genetics*

Substances

  • Antimetabolites, Antineoplastic
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • Cytarabine