Inactivation of p53 and amplification of MYCN gene in a terminal lymphoblastic relapse in a chronic lymphocytic leukemia patient.
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.
Stano-Kozubik
Katerina
K
Department of Internal Medicine-Hematooncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Malcikova
Jitka
J
Tichy
Boris
B
Kotaskova
Jana
J
Borsky
Marek
M
Hrabcakova
Viera
V
Francova
Hana
H
Valaskova
Iveta
I
Bourkova
Ludmila
L
Smardova
Jana
J
Doubek
Michael
M
Brychtova
Yvona
Y
Pospisilova
Sarka
S
Mayer
Jiri
J
Trbusek
Martin
M
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*
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53