MDM2 and p53 in childhood acute lymphoblastic leukemia: higher expression in childhood leukemias with poor prognosis compared to long-term survivors.
In previous studies the authors have found increased expression of p53 and MDM2 proteins in leukemic cells in a majority of children eligible for bone marrow transplantation (BMT) due to relapse or prognostically unfavorable features. In this study the immunohistochemical expression of p53, MDM2, and p21Cip1 was investigated in bone marrow samples from the time of diagnosis in 30 children with acute lymphoblastic leukemia (ALL) surviving disease-free at least 5 years. This group was compared with 15 advanced ALL patients, admitted for BMT. In 7 of the BMT patients orginal diagnostic marrow samples were also available for analysis. Four out of 30 ALL patients in the relapse-free group expressed p53 in the original leukemic cell population, while 8/15 advanced ALL patients did before BMT (p = .014). Four out of 30 cases in the relapse-free group expressed MDM2, while 10/15 in the BMT group did (p = .0011). In retrospect, MDM2 overexpression at the time of diagnosis was also more common (p = .0098) in the BMT group as well as p53 overexpression (p = .054) compared to nonrelapsed patients.
Gustafsson
B
B
Department of Paediatrics, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. britt.gustafsson@klinvet.ki.se
Axelsson
B
B
Gustafsson
B
B
Christensson
B
B
Winiarski
J
J
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism; D001853:Bone Marrow / Q000737:chemistry; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D009687:Nuclear Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012189:Retrospective Studies; D017741:Survivors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2