title: Inactivation of p53 and amplification of MYCN gene in a terminal lymphoblastic relapse in a chronic lymphocytic leukemia patient.
abstract: 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.
authors.affiliation: Department of Internal Medicine-Hematooncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Stano-Kozubik
authors.forename: Jitka
authors.initials: J
authors.lastname: Malcikova
authors.forename: Boris
authors.initials: B
authors.lastname: Tichy
authors.forename: Jana
authors.initials: J
authors.lastname: Kotaskova
authors.forename: Marek
authors.initials: M
authors.lastname: Borsky
authors.forename: Viera
authors.initials: V
authors.lastname: Hrabcakova
authors.forename: Hana
authors.initials: H
authors.lastname: Francova
authors.forename: Iveta
authors.initials: I
authors.lastname: Valaskova
authors.forename: Ludmila
authors.initials: L
authors.lastname: Bourkova
authors.forename: Jana
authors.initials: J
authors.lastname: Smardova
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.forename: Yvona
authors.initials: Y
authors.lastname: Brychtova
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.forename: Martin
authors.initials: M
authors.lastname: Trbusek
mesh_terms: D005784:Gene Amplification; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D012008:Recurrence; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53