Elevated p53 protein expression; a predictor of relapse in rare chronic myeloid malignancies in children?
BACKGROUND
Alterations in the tumor suppressor gene TP53 have been associated with poor outcome in adult hematological malignancies. We have earlier reported an increased expression of the TP53 encoded protein p53, in bone marrow samples from pediatric patients with aggressive leukemia. Our aim was now to evaluate p53 protein expression at different time points before and after hematopoietic stem cell transplantation (HSCT) as a predictor of relapse in a group of children diagnosed with MDS, JMML and CML, and also investigate if potential alterations in expression could be correlated to mutations in TP53.


METHODS
Paraffin embedded bone marrow samples from 33 pediatric patients diagnosed with MDS, JMML and CML between 1997 and 2010 were collected retrospectively from time of diagnosis and pre and post HSCT. Immunohistochemistry (IHC) was performed on tissue microarrays (TMA) with antibodies to p53 and p21. DNA sequencing of exon 2-11 of TP53 was performed in 7 patients with JMML and 5 patients with MDS.


RESULTS
Elevated p53 protein expression at diagnosis predicted for relapse, odds ratio (OR) 1.19 (95% CI: 1.02-1.40, p = .028). Sequencing of TP53 did not reveal any mutations in the 12 patients analyzed and p53 expression correlated positively to p21 expression indicating a functional p53/p21 protein pathway.


CONCLUSIONS
Elevated p53 protein expression at diagnosis may be an indicator of relapse in children with MDS, JMML and CML.
1Department of Pediatrics, Astrid Lindgren Children`s Hospital, Karolinska University Hospital-Huddinge, Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
Emma
E
Honkaniemi
Kristin
K
Mattsson
Gisela
G
Barbany
Birgitta
B
Sander
Britt
B
Gustafsson
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011237:Predictive Value of Tests; D012008:Recurrence; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53