[Update hepatitis D]. / Update Hepatitis D.

The relevance of chronic hepatitis delta results from its high morbidity. Prevalence of hepatitis D decreases in classic endemic areas of the Mediterranean Basin, but increases in Eastern European countries. Hepatitis D is mainly a disease of immigrants in Germany. Hepatitis D virus (HDV) is an incomplete virus, which needs the hepatitis B surface protein (HBsAg) but not hepatitis B virus (HBV) replication for its propagation. In case of HBsAg detection a screening for HDV antibodies should be performed. Simultaneous HDV/HBV infection leading to spontaneous virus clearance in the majority of cases has to be differentiated from HDV superinfection with a high rate of chronification. Chronic hepatitis D is difficult to treat. Treatment regimens for hepatitis D are interferon-based so far. Pegylated interferons, a prolongation of treatment beyond 12 months, combination therapies with ribavirin and prenylation inhibitors are possibly new therapeutic options in chronic hepatitis C.

Gene expression patterns in acute myeloid leukemia correlate with centrosome aberrations and numerical chromosome changes.

Centrosomes, which mediate accurate chromosome segregation during mitosis, undergo duplication precisely once per cell division at the G1/S boundary. Recently, we described centrosome aberrations as a possible cause of aneuploidy in acute myeloid leukemia (AML) and found a correlation of the percentage of cells carrying abnormal centrosomes to their cytogenetic risk profile. To elucidate the molecular events responsible for the development of centrosome aberrations in AML, tumor RNA of 29 AML samples was hybridized to cDNA microarrays. The microarrays comprised some 2800 different genes with relevance to hematopoiesis, tumorigenesis and mitosis and included a set of 359 centrosome-associated genes. We identified two gene expression signatures, which allowed an accurate classification according to the extent of centrosome aberrations and the ploidy status in 28 of 29 patients each. Specifically, 18 genes were present in both signatures, including genes that code for cell cycle regulatory proteins (cyclin A2, cyclin D3, cyclin H, CDK6, p18INK4c, p21Cip1, PAK1) and centrosome-associated proteins (pericentrin, alpha2-tubulin, NUMA1, TUBGCP2, PRKAR2A). In conclusion, the high expression of centrosome-associated genes matches the description of centrosome aberrations in several tumor types. Moreover, in AML the identification of G1/S-phase stimulatory genes suggests that one mechanism of aneuploidy induction might be the deregulation of centrosome replication at the G1/S boundary.

High rate of centrosome aberrations and correlation with proliferative activity in patients with untreated B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (CLL) is characterized by a high rate of clonal genomic alterations and a low proliferative activity with cell cycle arrest in G(0)/G(1) phase. Recently, centrosome aberrations have been described as a possible cause of chromosomal instability and aneuploidy in many human malignancies. To investigate whether centrosome aberrations do occur in CLL and whether they correlate with common prognostic factors and disease activity, we examined peripheral blood mononuclear cells (PBMC) from 70 patients with previously untreated CLL using an antibody to gamma-tubulin. All 70 CLL samples displayed significantly more cells with centrosome aberrations (median: 26.0%, range 11.0-41.5%) as compared to peripheral blood B lymphocytes from 20 age-matched, healthy individuals (median: 2.0%, range 0-6%; p < 0.001). The extent of centrosome aberrations correlated with the proliferative activity of the CLL cases as measured by lymphocyte doubling time (p = 0.02) as well as with time to first treatment (p = 0.05). Accordingly, more centrosome aberrations were found in PHA-stimulated T lymphocytes from healthy individuals as well as in B cells from surgically removed tonsil tissue of patients with acute tonsillitis as compared to the peripheral blood B lymphocytes from the control group. In contrast, no correlation was observed between centrosome aberrations and immunoglobulin VH gene mutation status or cytogenetically defined risk groups. These findings suggest that, despite the common observation of most CLL cells remaining in G(0)/G(1) phase, their centrosome replication process is deregulated and correlates to the proliferative activity of CLL cells.

Centrosome aberrations in acute myeloid leukemia are correlated with cytogenetic risk profile.

Genetic instability is a common feature in acute myeloid leukemia (AML). Centrosome aberrations have been described as a possible cause of aneuploidy in many human tumors. To investigate whether centrosome aberrations correlate with cytogenetic findings in AML, we examined a set of 51 AML samples by using a centrosome-specific antibody to pericentrin. All 51 AML samples analyzed displayed numerical and structural centrosome aberrations (36.0% +/- 16.6%) as compared with peripheral blood mononuclear cells from 21 healthy volunteers (5.2% +/- 2.0%; P <.0001). In comparison to AML samples with normal chromosome count, the extent of numerical and structural centrosome aberrations was higher in samples with numerical chromosome changes (50.5% +/- 14.2% versus 34.3% +/- 12.2%; P <.0001). When the frequency of centrosome aberrations was analyzed within cytogenetically defined risk groups, we found a correlation of the extent of centrosome abnormalities to all 3 risk groups (P =.0015), defined as favorable (22.5% +/- 7.3%), intermediate (35.3% +/- 13.1%), and adverse (50.3% +/- 15.6%). These results indicate that centrosome defects may contribute to the acquisition of chromosome aberrations and thereby to the prognosis in AML.