Inactivation of p53 and amplification of MYCN gene in a terminal lymphoblastic relapse in a chronic lymphocytic leukemia patient
| Autor: | Jitka Malčíková, Iveta Valášková, Ludmila Bourková, Katerina Stano-Kozubik, Jana Šmardová, Marek Borsky, Hana Skuhrová Francová, Šárka Pospíšilová, Martin Trbušek, Jana Kotašková, Michael Doubek, Viera Hrabčáková, Yvona Brychtová, Jiri Mayer, Boris Tichy |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research Somatic cell Chronic lymphocytic leukemia Somatic hypermutation Malignancy 03 medical and health sciences 0302 clinical medicine Recurrence hemic and lymphatic diseases Genetics medicine Humans Prolymphocytic leukemia Molecular Biology 030304 developmental biology Oncogene Proteins N-Myc Proto-Oncogene Protein 0303 health sciences biology Gene Amplification Nuclear Proteins Cytidine deaminase Middle Aged medicine.disease Leukemia Lymphocytic Chronic B-Cell 3. Good health Lymphoma 030220 oncology & carcinogenesis Immunology Cancer research biology.protein Somatic Hypermutation Immunoglobulin Tumor Suppressor Protein p53 Antibody |
| Zdroj: | Cancer Genetics and Cytogenetics. 189:53-58 |
| ISSN: | 0165-4608 |
| Popis: | B-cell chronic lymphocytic leukemia (CLL) is an incurable disease with a highly variable clinical course. A proportion of patients eventually progress to a higher stage of malignancy. A recent association has been observed between the presence of aberrant somatic hypermutations in leukemic cells (hypermutations occurring outside of the immunoglobulin locus) and the transformation to a diffuse large B-cell lymphoma or prolymphocytic leukemia. In this study, we report on the rarely observed blastic transformation in a CLL patient who had previously been shown to harbor aberrant somatic hypermutations in the TP53 tumor-suppressor gene (Mol Immunol 2008;45:1525-29). The enzyme responsible, the activation-induced cytidine deaminase, was still active within the transformation, as evidenced by the ongoing class-switch recombination of cytoplasmic immunoglobulins. The transformation was accompanied by a complete p53 inactivation, as well as complex karyotype changes including prominent amplification of MYCN oncogene. Our case-study supports the view that the aberrant somatic hypermutation is associated with transformation of CLL to a more aggressive malignancy. |
| Databáze: | OpenAIRE |
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