Overexpression of MDM2 in acute childhood lymphoblastic leukemia.
Mutation of the TP53 gene is one of the most common molecular alterations in a variety of tumors, but it occurs infrequently in childhood and adult hematological malignancies. Protein accumulation often results from mutations that lead to inactivation of the p53 protein. Other causes of functional inactivation of the p53 protein include stabilization of p53 via proteins such as MDM2, an oncoprotein capable of forming specific complexes with p53. In the present study, protein expressions of MDM2 and p53 were investigated by immunohistochemistry from bone marrow samples in 23 patients with acute lymphoblastic leukemia aged 1-13 years at diagnosis. p53 protein overexpression was detected in only one case, while overexpression of MDM2 was detected in samples from five patients. All five patients overexpressing MDM2 belonged to a group with unfavorable prognostic signs at diagnosis and three of them relapsed or died within 6 months after diagnosis.
Gustafsson
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Department of Paediatrics, Huddinge Hospital, Karolinska Institute, Huddinge, Sweden. leif.gustafsson@mbox301.swipnet.se
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Gustafsson
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D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor; D002648:Child; D002675:Child, Preschool; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2; D012008:Recurrence; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2