ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications

We evaluated the expression of 2 members of the Syk family, ZAP-70 and Syk, in acute lymphoblastic leukemia (ALL) samples, using data derived from a series of 33 T-ALL and 95 B-lineage adult ALL patients analyzed by oligonucleotide arrays. Of the B-lineage ALL cases, 37 were BCR/ABL+, 10 were ALL1/AF4+, 5 were E2A/PBX1+, and 43 carried no known molecular abnormality. ZAP-70 was highly expressed in T-ALL. A high ZAP-70 expression was also found in a proportion of B-lineage ALL, the highest levels being associated with the E2A/PBX1+ group and the lowest with ALL1/AF4+ cases (P < .001). A higher ZAP-70 expression was also observed in the pre-B group (P < .001). Remarkably, Syk expression was always preserved, suggesting that ZAP-70 expression is not substitutive of Syk. At the protein level, ZAP-70 was evaluated on 39 newly diagnosed ALL patients (25 adults, 14 children) and was detected in 23 cases (59%). ZAP-70 expression was consistently found in Ig mu+ cases. Evaluation of long-term outcome in cases without molecular abnormalities showed that the higher levels of ZAP-70 were coupled to a higher relapse rate. In ALL, ZAP-70 expression is associated with the E2A/PBX1 rearrangement and pre-B stage and may have a prognostic role and be a candidate molecule for targeted therapies

Generation of functional dendritic cells (DC) in adult acute lymphoblastic leukemia: rationale for a DC-based vaccination program for patients in complete hematological remission

The capacity to generate effective dendritic cells (DC) from adult acute lymphoblastic leukemia (ALL) patients in complete remission (CR) and off-therapy was investigated. Monocyte-derived DC cultured in the presence of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4 and tumor necrosis factor (TNF)-alpha expressed maturation markers, produced IL-12 and loaded apoptotic bodies to a similar extent to normal DC. Patients' circulating T and NK lymphocytes were normally represented and, after stimulation, were capable of producing TNF-alpha and interferon-gamma to a similar extent to control lymphocytes. DC loaded with leukemia-derived apoptotic bodies increased their ability to stimulate both allogeneic and autologous lymphocytes, and to generate specific anti-leukemic CD3 + cells. These findings offer a rationale for the design of DC-based vaccine programs for adult ALL patients in CR with the aim of controlling/eradicating the disease

Current challenges and future perspectives for the full circular economy of water in European countries

This paper reviews the current problems and prospects to overcome circular water economy management challenges in European countries. The geopolitical paradigm of water, the water economy, water innovation, water management and regulation in Europe, environmental and safety concerns at water reuse, and technological solutions for water recovery are all covered in this review, which has been prepared in the frame of the COST ACTION (CA, 20133) FULLRECO4US, Working Group (WG) 4. With a Circular Economy approach to water recycling and recovery based on this COST Action, this review paper aims to develop novel, futuristic solutions to overcome the difficulties that the European Union (EU) is currently facing. The detailed review of the current environmental barriers and upcoming difficulties for water reuse in Europe with a Circular Economy vision is another distinctive aspect of this study. It is observed that the biggest challenge in using and recycling water from wastewater treatment plants is dealing with technical, social, political, and economic issues. For instance, geographical differences significantly affect technological problems, and it is effective in terms of social acceptance of the reuse of treated water. Local governmental organizations should support and encourage initiatives to expand water reuse, particularly for agricultural and industrial uses across all of Europe. It should not also be disregarded that the latest hydro politics approach to water management will actively contribute to addressing the issues associated with water scarcity

Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol

Between 1996 and 2000, 90 newly diagnosed adult patients with T-acute lymphoblastic leukemia (T-ALL) were registered in the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acuta Limfoide (LAL) 0496 protocol. Cases were centrally processed for morphology, immunophenotype, cytogenetics, molecular biology, and multidrug resistance (MDR). Twenty-two patients were females and 68 were males. Four percent of cases were pro-T, 47% pre-T, 39% cortical T, and 10% mature T-ALL. Fifty-six percent of patients with pro-T + pre–T-ALL achieved complete remission (CR) compared with 91% for cortical + mature cases (P = .002). CD34 expression was associated with a significantly lower CR rate: 54% versus 84% (P = .009). Thirty-one (36.5%) of 85 patients had an abnormal karyotype, the most common abnormality (15%) being a partial del(6q). The cytogenetic profile did not impact on CR achievement. MDR1 function, present in 26% of cases, correlated significantly with CR achievement (P = .004). A highly significant (P = .001) difference in CR rate was observed between patients who did not express the CD13/CD33/CD34 antigens and were MDR functionally negative (96%) compared with patients positive for at least one of these markers (57%). Multivariate analysis showed an impact on CR achievement for CD33 expression and MDR1 function. An extensive biologic workup of adult T-ALL cases at presentation is recommended in order to design tailored therapeutic strategies aimed at improving CR rates

Reduced susceptibility to apoptosis correlates with kinetic quiescence in disease progression of chronic lymphocytic leukaemia

The role of apoptosis and cell kinetics in the mechanisms of disease progression of chronic lymphocytic leukaemia (CLL) is still unclear. In the present study, we investigated the susceptibility of leukaemic cells taken from 75 CLL patients with either stable (STD) or progressive disease (PRD) to enter apoptosis. Particular attention was paid to the relationship between cell cycle status and autologous serum (AS). The susceptibility to enter apoptosis was significantly greater in STD than in PRD, both in standard medium (mean = 23.62% +/- 14.7 versus 14.23% +/- 7.2; P = 0.02) and in the presence of AS (mean = 23.03% +/- 17.9 versus 11.27% +/- 7.6; P = 0.01). Furthermore, cell kinetics studies revealed a higher quiescence in PRD than in STD cases, both in terms of a lower RNA content (P = 0.04) and of higher expression of the negative cell cycle regulator p27(kip1) (P = 0.03). These kinetic differences were confirmed by short-term in vitro culture both in fetal calf serum and in AS. The results of this study indicate that CLL cells from PRD cases are characterized by a higher degree quiescence and much lower susceptibility to apoptosis when compared with STD ones. In this context, AS does not appear to play a specific role. The association between these kinetic characteristics and disease progression in CLL prompts further studies to establish whether higher quiescence may be responsible for the decreased susceptibility of PRD cells to enter apoptosis