title: Cytogenetic, FISH, and molecular studies in a case of B-cell chronic lymphocytic leukemia with karyotypic evolution.
abstract: We report the clinical, cytogenetic, fluorescence in situ hybridization (FISH) and molecular findings in a 54-yr-old male patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL), who showed progression to a diffuse large B-cell lymphoma (Richter's syndrome). Genetic studies were performed at diagnosis and during the Richter's transformation (RT). A clonal karyotype with two dicentric chromosomes, psu dic(12,21)(q24;q10) and dic(17,18)(p11.2;p11.2), was found. Both rearrangements were confirmed by FISH. Molecular cytogenetics analysis using p53 probe showed monoallelic loss of this tumor suppressor gene in 43.8% and 77.3% of cells for the first and the second studies, respectively). In both studies, deletions of D13S319 (18% and 12% of cells) and D13S25 loci (13% and 12% of cells) at 13q14 were found. Polymerase chain reaction analysis showed the MBR/JH rearrangement of the bcl-2 gene. FISH studies using LSI bcl-2/IgH probe allowed quantifying the clonal cell population with this rearrangement (4% and 6.6% of cells at diagnosis and RT, respectively). To our knowledge, this is the first case with a psu dic(12,21) described in B-CLL. The low percentage of cells with the 13q14 deletion and bcl-2/IgH rearrangement suggests that they were secondary events that resulted from clonal evolution. Our patient had a short survival (9 months) and a clear lack of response to several therapeutic agents, confirming the association of p53 gene deletion and karyotypic evolution with disease progression.
authors.affiliation: Department of Genetics, Instituto de Investigaciones Hematológicas 'Mariano R. Castex', Academia Nacional de Medicina, Buenos Aires, Argentina. cpchena@hematologia.anm.edu.ar
authors.forename: Christian
authors.initials: C
authors.lastname: Chena
authors.forename: Roxana
authors.initials: R
authors.lastname: Cerretini
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Noriega
authors.forename: Marina
authors.initials: M
authors.lastname: Narbaitz
authors.forename: Mariano
authors.initials: M
authors.lastname: Scolnik
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Palacios
authors.forename: Daniela
authors.initials: D
authors.lastname: Neme
authors.forename: Salvador
authors.initials: S
authors.lastname: Bruno
authors.forename: Irma
authors.initials: I
authors.lastname: Slavutsky
mesh_terms: D020732:Cytogenetic Analysis / Q000379:methods*; D018450:Disease Progression; D017353:Gene Deletion; D015321:Gene Rearrangement; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction