Standardization of BCR-ABL1 p210 Monitoring: From Nested to Digital PCR

The introduction of tyrosine kinase inhibitors in 2001 as a targeted anticancer therapy has significantly improved the quality of life and survival of patients with chronic myeloid leukemia. At the same time, with the introduction of tyrosine kinase inhibitors, the need for precise monitoring of the molecular response to therapy has emerged. Starting with a qualitative polymerase chain reaction, followed by the introduction of a quantitative polymerase chain reaction to determine the exact quantity of the transcript of interest-p210 BCR-ABL1, molecular monitoring in patients with chronic myeloid leukemia was internationally standardized. This enabled precise monitoring of the therapeutic response, unification of therapeutic protocols, and comparison of results between different laboratories. This review aims to summarize the steps in the diagnosis and molecular monitoring of p210 BCR-ABL1, as well as to consider the possible future application of a more sophisticated method such as digital polymerase chain reaction

Pilot Scale Evaluation of Wild Saccharomyces cerevisiae Strains in Aglianico

In winemaking, the influence of Saccharomyces cerevisiae strains on the aromatic components of wine is well recognized on a laboratory scale, but few studies deal with the comparison of numerous strains on a pilot scale fermentation. In this scenario, the present work aimed to validate the fermentative behavior of seven wild S. cerevisiae strains on pilot-scale fermentations to evaluate their impact on the aromatic profiles of the resulting wines. The strains, isolated from grapes of different Italian regional varieties, were tested in pilot-scale fermentation trials performed in the cellar in 1 hL of Aglianico grape must. Then, wines were analyzed for their microbiological cell loads, main chemical parameters of enological interest (ethanol, total sugars, fructose, glucose, total and volatile acidity, malic and lactic acids) and volatile aroma profiles by GC/MS/SPME. Seventy-six volatile compounds belonging to six different classes (esters, alcohols, terpenes, aldehydes, acids, and ketones) were identified. The seven strains showed different trends and significant differences, and for each class of compounds, high-producing and low-producing strains were found. Since the present work was performed at a pilot-scale level, mimicking as much as possible real working conditions, the results obtained can be considered as a validation of the screened S. cerevisiae strains and a strategy to discriminate in real closed conditions strains able to impart desired wine sensory features

Variable but consistent pattern of Meningioma 1 gene (MN1) expression in different genetic subsets of acute myelogenous leukaemia and its potential use as a marker for minimal residual disease detection

Meningioma 1 (MN1) gene overexpression has been reported in acute myeloid leukaemia (AML) patients and identified as a negative prognostic factor. In order to characterize patients presenting gene overexpression and to verify if MN1 transcript could be a useful marker for minimal residual disease detection, MN1 was quantified in 136 AML patients with different cytogenetic risk and in 50 normal controls. In 20 patients bearing a fusion gene transcript suitable for minimal residual disease quantitative assessment and in 8 patients with NPM1 mutation, we performed a simultaneous analysis of MN1 and the fusion-gene transcript or NPM1 mutation during follow-up. Sequential MN1 and WT1 analysis was also performed in 13 AML patients lacking other molecular markers. The data obtained show that normal cells consistently express low levels of MN1 transcript. In contrast, high levels of MN1 expression are present in 47% of patients with normal karyotype and in all cases with inv(16). MN1 levels during follow-up were found to follow the pattern of other molecular markers (fusion gene transcripts, NPM1 and WT1). Increased MN1 expression in the BM during follow up was always found to be predictive of an impending hematological relapse

Early prediction of treatment outcome in acute myeloid leukemia by measurement of WT1 transcript levels in peripheral blood samples collected after chemotherapy

The Wilms' tumor gene WT1 is a reliable marker for minimal residual disease assessment in acute leukemia patients. The study was designed to demonstrate the potential use of WT1 to establish quality of remission in acute leukemia patients for early identification of patients at high risk of relapse. A prospective study based on a quantitative Real-Time PCR (TaqMan) assay in 562 peripheral blood samples collected from 82 acute leukemia patients at diagnosis and during follow-up was established. The evaluation of WT1 in peripheral blood samples after induction chemotherapy can distinguish the continuous complete remission patients from those who obtain only an "apparent" complete remission and who could relapse within a few months. WT1 helps identify patients at high risk of relapse soon after induction chemotherapy allowing post-induction therapy in high risk patients to be intensified

Effects of initial-state dynamics on collective flow within a coupled transport and viscous hydrodynamic approach

We evaluate the effects of preequilibrium dynamics on observables in ultrarelativistic heavy-ion collisions. We simulate the initial nonequilibrium phase within A MultiPhase Transport (AMPT) model, while the subsequent near-equilibrium evolution is modeled using (2+1)-dimensional relativistic viscous hydrodynamics. We match the two stages of evolution carefully by calculating the full energy-momentum tensor from AMPT and using it as input for the hydrodynamic evolution. We find that when the preequilibrium evolution is taken into account, final-state observables are insensitive to the switching time from AMPT to hydrodynamics. Unlike some earlier treatments of preequilibrium dynamics, we do not find the initial shear viscous tensor to be large. With a shear viscosity to entropy density ratio of $0.12$, our model describes quantitatively a large set of experimental data on Pb+Pb collisions at the Large Hadron Collider(LHC) over a wide range of centrality: differential anisotropic flow $v_n(p_T) ~(n=2-6)$, event-plane correlations, correlation between $v_2$ and $v_3$, and cumulant ratio $v_2\{4\}/v_2\{2\}$.Comment: 10 pages, v2: minor revisio