Christian Chena

Biallelic deletion 13q14.3 in patients with chronic lymphocytic leukemia: cytogenetic, FISH and clinical studies

Background and objective:  Monoallelic deletion of 13q14.3 (13q14x1) is the most common abnormality in chronic lymphocytic leukemia (CLL). As a sole alteration, it predicts a favorable outcome. Biallelic 13q14.3 (13q14x2) deletion or concomitant 13q14x1/13q14x2 has been scarcely evaluated in the literature. We present the clinical, cytogenetic and fluorescence in situ hybridization (FISH) analysis of six CLL patients with normal karyotypes and 13q14x2 and their comparison to cases with 13q14x1 as a single abnormality.

Interphase cytogenetic analysis in Argentinean B-cell chronic lymphocytic leukemia patients: association of trisomy 12 and del(13q14)

We have evaluated genomic aberrations by conventional cytogenetics and fluorescence in situ hybridization (FISH) analysis in a series of 57 Argentinean B-cell chronic lymphocytic leukemia (B-CLL) patients. The studies were performed on stimulated peripheral blood lymphocytes. FISH analysis for trisomy 12, 13q14 deletion, and monosomy of TP53 (also known as p53) was performed according to standard protocols. Our results showed 46.3% of patients with clonal chromosomal alterations by conventional cytogenetics and 80.7% by FISH. Trisomy 12 was found in 21.9% of patients by G-banding analysis and in 35% by FISH studies. Allelic loss of 13q14 was observed in 63.2% patients, most of them showing D13S319 and D13S25 deletion; 11% of patients showed TP53 monosomy. Coexistence of trisomy 12 and 13q14 deletion was found in 17.5% of patients. In this group, deletion 13q14 was the prevalent clone, with percentages 25-35% higher than those observed for trisomy 12, suggesting clonal evolution. The coexistence of trisomy 12 with deletion 13q14 was observed in a higher frequency than reported in the literature. A probable adverse prognosis is suggested for this group of patients, likely related to clonal evolution.

Evaluation of constitutional chromosome aberrations in hematologic disorders

We have reviewed 4164 patients with various hematologic disorders cytogenetically studied in our laboratory during the last 25 years to analyze the frequency of constitutional chromosome aberrations (CCA) and to evaluate their association with hematologic malignancies. Our population of patients included 1133 pediatric patients and 3031 adults. Twenty-four (0.58%) cases showed CCA. They included four patients with Robertsonian translocations, one patient with a balanced translocation, two patients with sex chromosome abnormalities, and 17 cases with Down syndrome (DS). Nonsignificant differences among the frequency of patients with CCA from our hematologic series and those observed in the two largest combined surveys of livebirth published (0.65-0.84%) were found. The incidence of DS patients in our population (0.41%) was approximately three times higher than of that observed at birth (0.12-0.17%; P<0.001). The total incidence of constitutional chromosome abnormalities in the non-DS hematologic patients was 0.168% (7 of 4164) lower than of that observed in the newborn population (0.51-0.67%; P<0.001). Nonsignificant differences were found when the incidences of structural aberrations and sex chromosome anomalies were individually compared with the data of the overall population. Our results suggest that the presence of a CCA, other than DS, would not predispose patients to hematologic malignancies.

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 (Richters syndrome). Genetic studies were performed at diagnosis and during the Richters 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.

Structural aberrations of chromosomes 17 and 12 in chronic B-cell disorders.

Abstract: Objectives: Genomic aberrations can now be identified in approximately 80% of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients. In the present study, four new structural changes involving chromosomes 17 and 12 in CLL/SLL patients are described.

dup(12)(q13–q22) and 13q14 Deletion in a Case of B-Cell Chronic Lymphocytic Leukemia

Cases with partial trisomy 12 have rarely been found in B-cell chronic lymphocytic leukemia (CLL). We report our clinical, cytogenetic and fluorescence in situ hybridization (FISH) findings in a CLL patient with a duplication of part of the long arm of chromosome 12 between bands q13–q22. This patient was the only case with this duplication among the 112 cases (0.9%) of CLL cytogenetically analyzed in our laboratory. FISH studies using unique-sequence specific probes for the RB-1 (retinoblastoma) gene and the D13S319 locus at the 13q14 band showed a monoallelic loss for the D13S319 locus (20% of cells) with a diploid RB-1 gene. Our case showed an atypical morphology (35% prolymphocytes), a high proliferation rate and progression of the disease, indicating that the duplication of this region may be equivalent to complete trisomy 12 in CLL patients.

CD8 Expression in a Case of Chronic Lymphocytic Leukemia with Trisomy 12

We report a case of B-cell chronic lymphocytic leukemia (B-CLL) with aberrant expression of the T-cell-associated antigen CD8, as revealed by two-color flow-cytometric analysis. DNA studies showed immunoglobulin heavy-chain gene rearrangement, but not of γ-chain T-cell receptor, confirming the B-cell origin of the neoplastic cells. Ploidy analysis showed a tetraploid population and high S-phase fraction. B-CLL cells also carried trisomy 12, detected by fluorescence in situ hybridization. The identification of more cases with the same features would be necessary to establish the prognosis of this subtype of B-CLL.