Experimental Evidence for Mobility/Immobility of Metals in Peat

The biogeochemical cycles of most toxic metals have been significantly altered by anthropogenic activities. Anaerobic, rain-fed organic soils are believed to record historical changes in atmospheric pollution. Suspected postdepositional mobility of trace elements, however, hinders the usefulness of peat bogs as pollution archives. To lower this uncertainty, we quantified the mobility of six trace metals in peat during an 18-month field manipulation. A replicated, reciprocal peat transplant experiment was conducted between a heavily polluted and a relatively unpolluted peatland, located 200 km apart in the Czech Republic (Central Europe). Both peatlands were Sphagnum-derived, lawn-dominated, and had water table close to the surface. A strikingly different behavior was observed for two groups of elements. Elements of group I, Fe and Mn, adjusted their abundances and vertical patterns to the host site, showing an extremely high degree of mobility. In contrast, elements of group II, Pb, Cu, Zn, and Ti, preserved their original vertical patterns at the host site, showing a high degree of immobility. Our experimental results suggest that not just lead, but also copper and zinc concentration profiles in peat are a reliable archive of temporal pollution changes within a wide pH range (2.55.8).JRC.E.5-Nuclear chemistr

Epigenetic Changes in CEBPα Gene and Xenotransplantation Model of B Cell Precursor Acute Lymphoblastic Leukemia Switching to Monocytoid Lineage During the Early Phase of the Treatment

Abstract Abstract 876 Immunophenotypic instability during early phase of ALL treatment is a frequent observation during flow cytometric minimal residual disease (FC MRD) monitoring. Antigens typically involved include CD10, CD20, CD34 and CD45 and these changes do not usually revoke initial disease classification and do not hamper FC MRD detection. We previously described a subtype of B-cell precursor (BCP) ALL with striking immunophenotypic instability towards monocytoid lineage within the first month of therapy (switching ALL-swALL). Blasts expressing both B and monocytoid markers emerged at early time points on days 8 and 15 of treatment while later only those blasts with pure monocytoid phenotype were present. Incidence of swALL in childhood was unexpectedly high (3-4% of all pediatric BCP ALL) as confirmed in two national reference labs. This phenomenon was associated with aberrant expression of CD2 (LFA-2) on diagnostic blasts (Mejstrikova et al, ASH 2010). The leukemic origin of monocytoid blasts was proven by the detection of clone-specific immunoreceptor gene rearrangements (Ig-TCR). No common genetics aberration was found in a cohort of swALL (n=17), MLL gene was always in germline configuration. We found an increased rate of alteration in IKZF1 gene compared to control BCP ALL cases (p=0.012). An expression analysis of the key hematopoietic regulators showed a difference in CEBPα expression, which is an important transcription factor in transdifferentiation of B cells into macrophages (Xie et al., Cell 2004). Expression of CEBPα is increased in swALL compared to other BCP ALL cases (p=0.01) already at diagnosis prior switching, however, the expression is lower compared to AML (p=0.002). We analyzed CEBPα the methylation status of the promoter region of this gene. Demethylation of CEBPα promoter region analyzed by bisulfite sequencing (295bp-594bp of promoter region) was found in 10/12 swALL cases, while it was seen in only 6/28 control BCP ALLs (Fisher test, p=0.0004). The only cases having demetylation in CEBPα were 5/5 BCR-ABLpos and 1/4 ETV6-RUNX1pos. Whole genome ERRBS method (Enhanced Reduced Representation Bisulfite Sequencing) confirmed this methylation pattern of CEBPα in 7 patients (4 swALL,3 BCP ALL). In order to establish an in vivo model to study the underlying molecular mechanisms, we transplanted ALL cells from 7 swALL patients intrafemorally into NOD-SCIDIL2Rgammanull (NSG) mice. Successfulstable engraftment was achieved only in 2 out of 7 swALL cases (28%) (Fisher test, p=0.049).Interestingly in these two cases, the 200 bp promoter region of CEBPα was methylated to some extent at diagnosis and completely methylated after engraftment into mice, suggesting the possibility of a selective advantage in this context. We treated engrafted animals with prednisolone and in both cases we observed demethylation of CEBPα promoter. Because the rate of engraftment of ALL in NSG is usually very high, these observations may indicate that the biology of this particular subset of patient is distinct. Conclusion: We described a novel subtype of BCP-ALL with the demethylation of CEBPα promoter region, increased CEBPα expression and immunophenotypic shift towards monocytic lineage during first weeks of the therapy. We identified CEBPα as the potential regulator of this lineage plasticity. Disclosures: No relevant conflicts of interest to declare

Care of patients with non-small-cell lung cancer stage III – the Central European real-world experience

Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements