A distinct p53 protein isoform signature reflects the onset of induction chemotherapy for acute myeloid leukemia.
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.
Anensen
Nina
N
Hematology Section, Institute of Medicine, University of Bergen, Norway
Oyan
Anne Margrete
AM
Bourdon
Jean-Christophe
JC
Kalland
Karl Henning
KH
Bruserud
Oystein
O
Gjertsen
Bjorn Tore
BT
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
D020033:Protein Isoforms; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53