Cytolytic function and survival of natural killer cells are severely altered in myelodysplastic syndromes.

Natural Killer (NK) cells are critical in host defense against malignant transformation and are potent antileukemic cytotoxic effectors. In the present study, we investigated the peripheral NK function in patients with myelodysplastic syndromes (MDS). We demonstrated that the peripheral NK cell population was quantitatively normal in MDS patients. Furthermore, NK cells displayed an expression of the activating natural cytotoxicity receptors (NCR) NKp46 and NKp30 as well as NKG2D similar to that observed in donors, but exert a highly decreased constitutive cytolytic activity compared to resting normal NK cells. Although activation with IL-2 resulted in the upregulation of NKp46 expression by MDS-NK cells, their cytolytic function remained deeply altered as compared to activated donor NK cells. In addition, MDS NK cells did not proliferate in vitro, and displayed an increased rate of apoptosis in response to IL-2 stimulation although the spontaneous apoptosis was not significantly increased. Interestingly, a proportion of peripheral MDS-NK cells were derived from the MDS clone as the cytogenetic anomaly found in bone marrow karyotype was also detected in 20-50% of circulating NK cells. In conclusion, NK cells' cytolytic function and proliferative capacities in response to activation by cytokines are profoundly altered in MDS.

Spatial and temporal variability of sediment deposition on artificial-lawn traps in a floodplain of the River Elbe.

Artificial-lawn mats were used as sediment traps in floodplains to measure sediment input and composition during flood events. To estimate the natural variability, 10 traps were installed during two flood waves at three different morphological units in a meander loop of the River Elbe. The geochemical composition of deposited and suspended matter was compared. The sediment input showed weak correlations with concentration and composition of river water. It also correlated poorly with flood duration and level as well as distance of trap position from the main river. This is due to the high variability of the inundation, different morphological conditions and the variability of sources. The composition of the deposits and the suspended matter in the river water was comparable. Hence, for the investigated river reach, the expected pollution of the floodplain sediments can be derived from the pollution of the suspended matter in the river during the flood wave.

Deposition, persistence and turnover of pollutants: First results from the EU project AquaTerra for selected river basins and aquifers.

Deposition, turnover and movement of persistent organic pollutants (POP) were investigated in the EU integrated project "AquaTerra", which is among the first funded environmental projects within the 6th Framework Program by the European Commission. Project work integrates across various disciplines that range from biogeochemistry, environmental engineering, computer modelling and chemistry to socio-economic sciences. Field study areas are the river basins of the Ebro, the Meuse, the Elbe and the Danube as well as the 3-km(2) French catchment of the Brévilles Spring. Within the first 2 years of the project more than 1700 samples of atmospherically deposited particles, sediments, and water have been collected in the above-mentioned systems. Results show clear spatial patterns of deposition of polyaromatic hydrocarbons (PAHs) with the highest rates in the Meuse Basin. For local inputs, in the Brévilles sandy aquifer, the contamination of the groundwater by the pesticides atrazine (AT) and deethylatrazine did not decrease even 5 years after their agricultural inputs were stopped. On the other hand, herbicides such as mecroprop (MCPP), and PAHs, were at least partially degraded microbiologically in laboratory studies with soils and aquifer material from selected sites. For sediment transport of contaminants, new flood sampling techniques revealed highest deposition rates of beta-hexachlorocyclohexane (beta-HCH) in river sediments at hotspot areas on the Mulde River in the Bitterfeld region (Elbe Basin, Germany). These selected preliminary results of AquaTerra help to improve fundamental understanding of persistent organic pollutants (POP) in the environment.

Myelodysplastic syndrome after acute promyelocytic leukemia: the European APL group experience.

With improved treatment of acute promyelocytic leukemia (APL) by all trans retinoic acid (ATRA) combined to anthracycline-aracytin chemotherapy (CT), a larger number of those patients may be at risk of late complications. Recently, the Rome group reported five cases of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML, non-APL) occurring during the course of 77 APL patients (6.5%) in complete remission (CR). From 1991 to 1998, we treated 677 newly diagnosed cases of APL, and 617 of them achieved CR with ATRA combined to CT (n=579) or CT alone (n=38); 246 of them received subsequent maintenance CT with 6 mercaptopurine and methotrexate. With a median follow-up of 51 months, 6 patients (0.97%) developed MDS, 13-74 months after the diagnosis of APL. In all six cases, t(15;17) and PML-RARalpha rearrangement were absent at the time of MDS diagnosis, and karyotype mainly showed complex cytogenetic abnormalities involving chromosomes 5 and/or 7, typical of MDS observed after treatment with alkylating agents, although none of the six patients had received such agents for the treatment of APL. Our findings suggest that MDS can indeed be a long-term complication in APL, although probably at lower incidence than that previously reported.