A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1).

Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report here a 20-year-old woman with severe transfusion-dependent anemia and reticulocytopenia. White blood cells and platelet counts were normal. Bone marrow examination showed a low percentage of erythroid precursors (6%) and a marked dyserythropoiesis and dysmegakaryopoiesis. A diagnosis of MDS (refractory anemia according to the FAB classification) with erythroid hypoplasia was made. Cytogenetic analysis of the bone marrow and peripheral blood revealed a 46,XX,t(3;14)(p21.1;q24.1) translocation, which was confirmed by fluorescence in situ hybridization analysis. This translocation was detected in the apparently healthy younger brother, father, and aunt (father's sister) of the patient. Clonality of T cells in the patient was not confirmed by the polymerase chain reaction and heteroduplex temperature-gradient gel electrophoresis. IgM serology for B19 parvovirus was negative. Other conditions known to be associated with erythroid hypoplasia, such as thymoma, were not present. The patient failed to respond to immunosuppressive therapy (antithymocyte globulin and cyclosporin A). Administration of recombinant human erythropoietin improved her anemia. To our knowledge, this balanced translocation, namely t(3;14)(p21.1;q24.1), which is present both in the patient with MDS with erythroid hypoplasia and in the healthy members of the family, has not been defined previously.

A different approach to telomere analysis with ddPRINS in chronic lymphocytic leukemia.

Telomeric sequences, located at the very end of the chromosomes, compensate for the chromosomal shortening as it happens after each round of cell division. Telomeric sequences influence the progress of cellular senescence and cancer progression. It has been reported that telomeres are shortened in acute leukemias where the cell turnover is high. B-cell chronic lymphocytic leukemia (CLL) is a particularly interesting haematological malignancy in regard to telomere dynamics because most of the malignant cells in CLL are mitotically inactive. In this study, we analysed the telomere length in patients with B-cell CLL in a comparison with the control group by using ddPRINS technique. Twenty patients with CLL and four healthy donors as a control group were included. We found short telomeres and no detectable telomeric repeats at the sites of chromosome fusion. We hypothesise that the telomeric erosion in CLL may reflect the dominance of malignant cells with an abnormally long life span. These cells may have encountered many antigenic stimulants in the past and hence underwent multiple clonal expansions. Our findings imply that shortened telomeres in CLL may be reflecting the "history" of the disease and serve as an independent prognostic factor.

Genotoxicity and sister chromatid exchange in patients with myelodysplastic disorders.

In this study, we aimed to evaluate genotoxicity by sister chromatid exchange frequency in the peripheral lymphocytes of patients with myelodysplastic syndrome (MDS). The study population consisted of 16 patients (females/males:6/10; mean age: 61.68 +/- 13.08 years) diagnosed with "refractory anemia" according to FAB classification. The results were compared with an age- and sex-matched control group. The sister chromatid exchange frequency in the study group was found to be significantly higher than the control group (8.3 +/- 11 vs. 6.83 +/- 1.07, P=0.0046). We suggest that increased DNA damage, which is revealed by the increased sister chromatid exchange in the present study may play a role in the etiopathogenesis of MDS.

Sister chromatid exchange and mitotic index in patients with cirrhosis related to hepatitis B and C viruses and in chronic carriers.

BACKGROUND/AIMS: It is controversial whether hepatitis B or C viruses induce liver cancer through non-specific mechanisms (inflammation and cell renewal) or direct genotoxicity. Considering that both viruses infect peripheral lymphocytes, studying sister chromatid exchange frequency and mitotic index in peripheral lymphocytes is a reasonable experimental approach to investigate their genotoxic potential separately. In the present study we investigated sister chromatid exchange frequency and mitotic index in the peripheral lymphocytes of patients with cirrhosis and chronic carriers with positive serology for HBV or HCV infections. METHODOLOGY: The study population consisted of 3 groups: group I involved 23 HBsAg positive chronic carriers; group II involved 30 HBsAg positive patients with cirrhosis and group III involved 9 HCV-positive patients with cirrhosis. The control group involved 30 healthy individuals. RESULTS: Sister chromatid exchange frequency was significantly higher in all the study groups than the control group (p < 0.05). The mitotic index was significantly lower in all the study groups than the control group (p < 0.05). CONCLUSIONS: The increased sister chromatid exchange frequency and low mitotic index may be reflecting a direct genotoxic effect of HBV and HCV in peripheral lymphocytes. We suggest that the same genotoxicity may also operate in the liver and contribute to hepatocarcinogenesis.