Emma Honkaniemi1, Kristin Mattsson, Gisela Barbany, Birgitta Sander, Britt Gustafsson. 1. 1Department of Pediatrics, Astrid Lindgren Children`s Hospital, Karolinska University Hospital-Huddinge, Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
Abstract
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. PROCEDURE: 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. CONCLUSION: Elevated p53 protein expression at diagnosis may be an indicator of relapse in children with MDS, JMML and CML.
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. PROCEDURE: 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. CONCLUSION: Elevated p53 protein expression at diagnosis may be an indicator of relapse in children with MDS, JMML and CML.
Authors: Sanam Loghavi; Alyaa Al-Ibraheemi; Zhuang Zuo; Guillermo Garcia-Manero; Mariko Yabe; Sa A Wang; Hagop M Kantarjian; Cameron C Yin; Roberto N Miranda; Raja Luthra; L Jeffrey Medeiros; Carlos E Bueso-Ramos; Joseph D Khoury Journal: Br J Haematol Date: 2015-06-30 Impact factor: 6.998
Authors: Stella Pearson; Baoqiang Guo; Andrew Pierce; Narges Azadbakht; Julie A Brazzatti; Stefano Patassini; Sonia Mulero-Navarro; Stefan Meyer; Christian Flotho; Bruce D Gelb; Anthony D Whetton Journal: J Proteome Res Date: 2019-11-12 Impact factor: 4.466