Irma Slavutsky

Telomere shortening in patients with plasma cell disorders

Abstract: Objectives: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).

Sister chromatid exchange in malignant lymphomas

Sister chromatid exchange (SCE) was evaluated in peripheral lymphocytes from 20 untreated patients with malignant lymphomas: 6 with Hodgkins disease (HD), 14 with non-Hodgkin lymphoma (NHL), and 5 with lymphadenitis. The mean SCE frequency (+/- SE) was: 11.2 +/- 0.6, 11.0 +/- 0.6, and 7.2 +/- 0.3 for HD, NHL, and lymphadenitis patients, respectively, and 8.7 +/- 0.2 for the control group. No differences in SCE score were observed in HD and NHL. These results allowed us to consider both groups (HD and NHL) as a single neoplastic population (mean +/- SE, 11.0 +/- 0.4). No significant differences were found between the lymphadenitis and control groups. On the other hand, significantly higher SCE scores were seen in neoplastic populations than in the control and lymphadenitis groups (p less than 0.001 and p less than 0.01, respectively). When SCE was compared by chromosome number and group between neoplastic patients and controls, a higher SCE frequency was observed in chromosomes #1, #2, #3, and B, C + X, E, F chromosome groups than in controls. SCE levels were significantly higher in lymphoma patients in all chromosome numbers and groups mentioned than in patients with lymphadenitis. It is suggested that the high SCE rate in the malignant lymphoma population is possibly related to an increased chromosomal instability.

Cytogenetic and immunologic phenotype findings in hodgkin's disease

There are very few chromosome studies using banding techniques of lymph nodes in Hodgkins disease (HD), and determinations of immunologic phenotypes are scarce. We have performed both cytogenetic and immunologic studies in 12 of 22 lymph node biopsies of different histologic types obtained from 20 HD patients (no mitotic cells were found in the remaining ten lymph nodes). A near-diploid modal number was obtained in 80% of the cases, and 20% showed a bimodal distribution. Clones were observed in 50% of HD lymph nodes, with chromosome markers in 60% of them. Markers 15q+, 5p-, and der(X) and a trisomy of chromosome #21 were observed in our cases. Seventy-one percent of the lymph nodes studied showed a predominance of T lymphocytes. Within the lymph nodes, where the karyotype was determined, 4/12 lymph nodes presented a predominance of B lymphocytes, and they were all included in the group with structural chromosome abnormalities.

Homogeneously staining regions (HSR) in a human malignant melanoma

A case of nodular malignant melanoma (level V of Clarks classification) with homogeneously staining regions (HSR) on the long arm of one chromosome #2 is described. Ultrastructural observation of melanosomic and promelanosomic granules near Golgis vesicles confirmed the histologic diagnosis. Chromosome analysis was performed on nine metaphases from a bone marrow sample and 76 metaphases from culture of the malignant skin tumor. G-banding revealed the presence of a clone with trisomy #8 and another cell line with the HSR marker. This is the first report of HSR in human melanoma cells. As HSR has been found only in malignant cells, we believe that among the many factors that influence the patients clinical evolution and poor response to treatment, the genic imbalance is of the utmost importance.

Abnormalities of chromosome No. 1: Two cases with lymphocytic lymphomas

Abstract Two cases of lymphocytic lymphoma with a duplication of part of the long arm of chromosome #1, between bands 1q25 and 1q32, are presented. The coincidence between this finding with others in the literature supports the concept that this specific chromosome segment is related to the proliferative advantage of malignant cells in neoplasia.

Cytogenetic, FISH, and molecular studies in a case of B‐cell chronic lymphocytic leukemia with karyotypic evolution

Abstract:u2002 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 (9u2003months) and a clear lack of response to several therapeutic agents, confirming the association of p53 gene deletion and karyotypic evolution with disease progression.

Translocation t(1;5) in a case of carcinoma of the cervix

We report a case of carcinoma of the cervix uteri, which presented both numerical and structural chromosome changes. The tumor showed the coexistence of lines with different modal chromosome numbers, but all of them with the t(1;5)(q25;132). We also observed the presence of double minutes, dicentric chromosomes, small acentric fragments, and/or tri- and quadriradial figures in 11% of the cells.

Sister chromatid exchanges in leukemic patients

Sister chromatid exchange (SCE) was studied in PHA-stimulated peripheral blood lymphocytes from 36 newly diagnosed and untreated leukemic patients: 16 with acute lymphoblastic leukemia (ALL), 10 with acute nonlymphocytic leukemia (ANLL), and 10 with chronic myelocytic leukemia (CML). The metaphases analyzed show no chromosomal abnormalities. The mean SCE frequency (mean +/- SE) for each group of patients was: 6.8 +/- 0.4, 6.6 +/- 0.3, and 7.0 +/- 0.6 per mitosis, respectively, which was significantly lower than the mean SCE score for 30 controls (8.7 +/- 0.2). No differences in SCE score among ALL, ANLL, and CML and a similar SCE frequency by chromosome number and group allowed consolidation of all the cases into a single group of 36 leukemic patients (6.8 +/- 0.3). When the frequency of SCE was compared by chromosome number and group between the leukemic patients with the control group, a significant decrease in SCE frequency was observed due to a low SCE score in almost all the complements, except chromosome #1. It is suggested that the low SCE rate is related to the leukemic process itself.

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.

Micronuclei induction by carboplatin in human lymphocyte subpopulations.

Micronuclei (MN) induction by carboplatin, cis-diammine-1,1-cyclobutane decarboxylate platinum (II) (CBDCA), in B and T lymphocytes was studied by the MAC (morphology/antibody/chromosome) method which allows the immunologic identification of different cell lineages. An increased frequency of MN in B and T lymphocytes in CBDCA-treated cultures compared with controls was observed (p < 0.001). CBD cells were found to be more sensitive to CBDCA damage. CBDCA-treated cultures showed a decrease, albeit statistically non-significant, in the proportion of CBD interphasic and mitotic cells. Furthermore, higher MN frequencies in isolated lymphocytes than in whole blood in both control and CBDCA-treated cultures were observed.