CD56, HLA-DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3-GLIS2 fusion transcript

The presence of CBFA2T3‐GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML‐CBFA2T3‐GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3‐GLIS2‐AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3‐GLIS2‐AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA‐DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak‐to‐negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA‐DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance

NUP98-fusion transcripts characterize different biological entities within acute myeloid leukemia: A report from the AIEOP-AML group.

In the last years, collaborative studies have joined to link the degree of genetic heterogeneity of acute myeloid leukemia (AML) to clinical outcome,1, 2 allowing risk stratification before therapy and guiding post-induction treatment of children with AML. So far, still half of these patients, whose disease is usually characterized by a grim prognosis, lack a known biomarker offering opportunities of targeted treatment

Acethylcholine esterase inhibitor tacrine reduced extinction responding, but not self-administration and drug discrimination, of nicotine or amphetamine in rats

Cholinergic transmission may play an important role in the mediation of drug addiction. Acethylcholine esterase (AChE) inhibitors (AChE-I) by increasing acethylcholine brain concentrations may offers a feasible tool to better understand the role of ACh in drug addiction behaviours. The aim of the series of experiments here described is to study the effect of AChE-I tacrine on three protocols of nicotine or d-amphetamine addictive behaviour in Sprague Dawley rats: drug discrimination, drug self administration and extinction responding. When different groups of rats met the criteria for d-amphetamine (0.6 mg/Kg IP) or nicotine (0.2 mg/Kg SC) discrimination from vehicle in a two-lever drug discrimination task, tacrine (1.25 mg/Kg, IP) was tested for generalization. The effect of tacrine pre-treatment (0.32 mg/Kg IV) on nicotine or amphetamine reinforcing properties was studied in two groups of rats trained to a schedule of FR2:d-amphetamine (0.1 mg/kg/infusion) or nicotine (0.03 mg/kg/infusion) IV self administration (1-h session). Finally, tacrine (0.32 mg/Kg IV) effect on responding on first extinction session was tested when amphetamine or nicotine IV infusions were omitted. Nicotine or amphetamine discriminative stimulus did not generalize with tacrine. Tacrine pre-treatment did not induce any change on nicotine or amphetamine self-administration. However, when given on the first day of extinction, tacrine induced a significant decrease of nicotine-paired (-63%, P<0.05) and a trend to decrease of amphetamine-paired (-50%, P=0.06 ) -lever responding vs. corresponding baseline. These findings showed that inhibition of AChE with tacrine did not change interoceptive and reinforcing stimuli properties of nicotine or amphetamine, but suggest a potential inhibitory effect on learning of the extinction responding. Further studies are needed to test tacrine on reinstatement to amphetamine or nicotine-seeking behaviour

Virtually pure near-infrared electroluminescence from exciplexes at polyfluorene/hexaazatrinaphthylene interfaces

Electronic processes at the heterojunction between chemically different organic semiconductors are of special significance for devices such as light-emitting diodes (LEDs) and photovoltaic diodes. Here, we report the formation of an exciplex state at the heterojunction of an electron-transporting material, a functionalized hexaazatrinaphthylene, and a hole-transporting material, poly(9,9-dioctylfluorene-alt-N-(4-butylphenyl)diphenylamine) (TFB). The energetics of the exciplex state leads to a spectral shift of ∼1 eV between the exciton and the exciplex peak energies (at 2.58 eV and 1.58 eV, respectively). LEDs incorporating such bulk heterojunctions display complete quenching of the exciton luminescence, and a nearly pure near-infrared electroluminescence arising from the exciplex (at ∼1.52 eV) with >98% of the emission at wavelengths above 700 nm at any operational voltag

Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming

Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and accumulation at tumor sites. Moreover, the observed Drp1-dependent imbalance toward a memory-like phenotype favors T cell exhaustion in the tumor microenvironment. All of these findings support a crucial role for Drp1 in several processes during T cell development and in anti-tumor immune-surveillance