title: A distinct p53 protein isoform signature reflects the onset of induction chemotherapy for acute myeloid leukemia.
abstract: OBJECTIVE
  The antioncogene protein product p53 has not been studied previously in cancer patients during in vivo chemotherapy. This study examined the early p53 protein and gene expression during induction chemotherapy in acute myeloid leukemia (AML).
  
  
  METHODS
  Leukemic cells were collected from five AML patients during their first 18 hours of induction chemotherapy and examined for p53 protein and gene expression by one- and two-dimensional gel immunoblot and high-density gene expression arrays.
  
  
  RESULTS
  Up-regulation of p53 protein expression was detected in AML patients posttreatment in vivo. One- and two-dimensional gel immunoblots showed two main forms of p53, denominated alpha p53 and delta p53, both recognized by various NH2-terminal directed antibodies. As a response to treatment, we detected rapid accumulation of alpha p53, with significantly altered protein expression levels already after 2 hours. The accumulation of alpha p53 was accompanied by increased transcription of putative p53 target genes and subsequent cytopenia in the patients.
  
  
  CONCLUSIONS
  Up-regulation of the p53 protein and target genes seems to be a prominent feature in induction chemotherapy of AML. The rapid shift from a shorter p53 protein form (delta) toward the full-length protein (alpha) underscores the complexity of p53 protein modulation in patients undergoing chemotherapy.
authors.affiliation: Hematology Section, Institute of Medicine, University of Bergen, Norway
authors.forename: Nina
authors.initials: N
authors.lastname: Anensen
authors.forename: Anne Margrete
authors.initials: AM
authors.lastname: Oyan
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bourdon
authors.forename: Karl Henning
authors.initials: KH
authors.lastname: Kalland
authors.forename: Oystein
authors.initials: O
authors.lastname: Bruserud
authors.forename: Bjorn Tore
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53